Electrical energy ablation systems, devices and methods for the treatment of tissue

ABSTRACT

A device for ablating target tissue of a patient with electrical energy is provided. An elongate shaft includes a proximal portion and a distal portion, and a radially expandable element is attached to the distal portion. An ablation element for delivering electrical energy to target tissue is mounted to the radially expandable element. The device can be constructed and arranged to ablate the duodenal mucosa of a patient while avoiding damage to the duodenal adventitial tissue. Systems and methods of treating target tissue are also provided.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/609,332 (Attorney Docket No. 41714-706.301), filed Jan. 29, 2015,which is a continuation of International Patent Application No.PCT/US2013/052786 (Attorney Docket No. 41714-706.601), filed Jan. 30,2013, which claims the benefit of U.S. Provisional Application Ser. No.61/677,422 (Attorney Docket No. 41714-706.101), filed Jul. 30, 2012, theentire content of which is incorporated herein by reference; thisapplication is also related to PCT Application Serial NumberPCT/US2012/021739 (Attorney Docket No. 41714-703-601), filed Jan. 18,2012; PCT Application Serial Number PCT/US2013/28082 (Attorney DocketNo. 41714-704.601), filed Feb. 27, 2013; and PCT Application SerialNumber PCT/US2013/37486, filed Apr. 19, 2013; the contents of each areincorporated herein by reference in their entirety.

TECHNICAL FIELD

The embodiments disclosed herein relate generally to systems, devicesand methods for treating tissue, particularly gastrointestinal tissue.

BACKGROUND

Diabetes is a metabolic disease in which a person develops high bloodsugar because the person's body does not produce enough insulin or thecells of the body are incapable of effectively responding to theproduced insulin. Primarily, diabetes is of two types: Type-1 andType-2. Type-1 diabetes results due to the body's failure to produceenough insulin, and Type-2 diabetes results from the body's autoimmunedestruction of pancreatic beta cells and, consequently, the body'sfailure to produce enough insulin, and Type 2 diabetes is a complexmetabolic derangement that causes hyperglycemia through insulinresistance (in which the body's cells fail to properly utilize theproduced insulin) and inadequate insulin production to meet the body'sneeds.

Currently, there are several procedures aimed at treating diabetes basedon the above concept. The procedures require major surgery, removal ofportions of the gastrointestinal (GI) tract, and/or placement of one ormore long-term implants. As with any major surgery, gastric bypasssurgery and device implant surgery carry a risk of complications.

Devices have been developed to deliver energy to the body. For example,cardiac ablation devices have been designed to deliver ablative energyto heart tissue. Additionally, urethral resection devices have beendesigned to burn or cut away portions of a prostate. Each of thesetechnologies has been modified and adapted toward effective usage in theparticular portion of the body to be treated, as well as the particulardisease to be treated.

There is a need for systems and methods that can provide a therapeutictreatment of the GI tract by the application of energy to the GI tract.Specifically, there is a need to provide a treatment of diabetes with aprocedure in the GI tract that is less invasive than gastric bypasssurgery and has other advantages for patients.

SUMMARY

According to one aspect of the present inventive concepts, a device forablating tissue of a patient with electrical energy includes an elongateshaft with a proximal portion and a distal portion; a radiallyexpandable element attached to the elongate shaft distal portion; and anablation element mounted to the radially expandable element andconfigured to deliver electrical energy to target tissue. The device isconfigured to ablate mucosal tissue (e.g. duodenal mucosal tissue orother small intestine mucosal tissue) while avoiding damagingadventitial tissue or other non-target tissue. The device can be furtherconfigured to ablate at least an inner layer of duodenal submucosaltissue and/or an inner layer of other mucosal tissue of the smallintestine. The device can be further configured to avoid ablating (e.g.not ablate) at least the outermost portion of submucosal tissue, such asto avoid ablating a layer comprising the outermost 100 microns, or theoutermost 200 microns of duodenal submucosal tissue. The device can befurther configured to ablate tissue such as: jejunal mucosal tissue;ileal mucosal tissue; and gastric mucosal tissue. The device can befurther configured to minimize damage to at least one of the pylorus orthe Ampulla of Vater, for example where the device includes anadvanceable sheath configured to minimize damage to at least one of thepylorus or the Ampulla of Vater. The device can be further configured toidentify the Ampulla of Vater. The device can include a fluid deliveryelement constructed and arranged to deliver fluid, gel or other materialinto submucosal tissue, such as to expand the submucosal tissue. Thefluid delivery element can comprise multiple fluid delivery elements,such as one or more needles and/or one or more fluid jets. The devicecan include one or more vacuum ports positioned proximate the multiplefluid delivery elements, such as to stabilize, manipulate or otherwiseapply a force to the tissue receiving the expansion material. Thesubmucosal tissue can be expanded to increase a target treatment area.The submucosal tissue can be expanded circumferentially.

The device can be constructed and arranged to perform a target tissuetreatment that modifies a tissue property selected from the groupconsisting of: a secretive property of a portion of the gastrointestinaltract; an absorptive property of a portion of the gastrointestinaltract; and combinations thereof.

The device can be further configured to minimize distension of duodenaltissue or other small intestine tissue. The device can be furtherconfigured to limit forces applied to a duodenal or other tissue wall,such as to limit forces to a level at or below 2.5 psi, or at or below 1psi. The device can be further configured to apply a force of at least0.2 psi to a tissue wall, or to apply a force of at least 0.5 psi to atissue wall. The device can be further configured to avoid damagingtissue selected from the group consisting of: a duodenal muscularislayer; jejunal muscularis layer; ileal muscularis layer; gastricmuscularis layer; Ampulla of Vater; bile duct; pancreas; pylorus;muscularis externae; serosa; and combinations of these. The device canbe further configured to ablate mucosal tissue in a curved segment ofthe small intestine, such as a curved segment of the duodenum. Thedevice can be further configured to ablate a tissue layer of at least500 microns. The device can be further configured to ablate a volume oftissue having a surface area and a depth, where the depth is less thanapproximately 1.0% its surface area, or less than approximately 0.1% itssurface area.

The elongate shaft of the device can be configured to be passed throughthe working channel of an endoscope. The shaft can have a diameter ofless than or equal to 6 mm, or less than or equal to 4.2 mm, or lessthan or equal to 3.8 mm, or less than or equal to 3.2 mm, or less thanor equal to 2.8 mm. The elongate shaft can be configured to passalongside an endoscope that has been placed in a gastrointestinal tract.The device can be configured for over-the-wire delivery, such asover-the-wire delivery through the gastrointestinal tract.

The device can be configured to treat substantially the entire length ofthe target tissue simultaneously, such as to treat the entire length ofthe duodenum simultaneously. The device can be configured to treat afirst length of small intestine (e.g. a first length of duodenum) in afirst energy application and a second length of small intestine (e.g. asecond length of duodenum) in a second energy application. In someembodiments, the first length of duodenum or other length of smallintestine overlaps the second length of duodenum or other length ofsmall intestine. In some embodiments, the first length of duodenum orother length of small intestine includes a first central axis and thesecond length of duodenum or other length of small intestine includes asecond central axis non-parallel with the first axis. The device can beconfigured to treat at least three lengths of small intestine with atleast three energy treatments, such as where the at least three lengthsof small intestine comprise at least 50% of the length of the duodenum.The device can be configured to deliver the electrical energy based on ameasured diameter of the small intestine, for example where the measureddiameter is measured by at least one radially expandable element of thedevice and/or by one or more radially expandable elements of a separatedevice.

The device radially expandable element can have a length less than orequal to approximately 20 mm. The radially expandable element can beconfigured to be relatively rigid during the delivery of the electricalenergy to the target tissue, for example where the ablation elementincludes multiple parallel conductors, and where the relatively rigidradially expandable element is configured to maintain spacing betweenthe multiple parallel conductors. The radially expandable element caninclude at least a portion that is round when expanded. The radiallyexpandable element can include at least a portion that, when expanded,includes a tissue-contacting shape selected from the group consistingof: triangle; rectangle; pentagon; hexagon; trapezoid; and combinationsof these. The tissue-contacting shape can be selected to allow anoperator to treat one or more target tissue portions without leavinggaps and/or to limit the number of repeated ablations needed to cover atarget tissue portion regularly or irregularly shaped area. The radiallyexpandable element can be configured to be folded to a radiallycompacted state from its radially expanded state. The radiallyexpandable element can be configured to linearize curvilineargastrointestinal tissue. The radially expandable element can beconfigured to distend gastrointestinal tissue.

In some embodiments, the radially expandable element includes a balloon,for example a compliant balloon, a non-compliant balloon, and/or apressure-thresholded balloon. The balloon can include an externalsurface and the ablation element can be mounted to the balloon externalsurface. The radially expandable element can further include a scaffoldbiased in a radially expandable condition. The device can furtherinclude at least one inflation lumen in fluid communication with theballoon.

In some embodiments, the radially expandable element includes a radiallyexpandable scaffold. Examples of radially expandable scaffolds include:an expandable cage; a stent-like structure; an array of splines; andcombinations of these. The radially expandable scaffold can includemultiple filaments configured to expand to a diameter of at least 20 mm,or at least 25 mm, or at least 30 mm, where the device includes a distalportion configured to be slidingly received by a channel with a diameterless than or equal to 6 mm. The radially expandable scaffold can includea scaffold resiliently biased in a radially expanded condition. Thedevice can further include a control shaft configured to expand theradially expandable scaffold when retracted. The radially expandablescaffold can include an array of splines, for example where the ablationelement includes at least a first electrode mounted to a first splineand a second electrode mounted to the first spline. Alternatively, theablation element includes at least a first electrode mounted to a firstspline and a second electrode mounted to a second spline. The radiallyexpandable scaffold can include an oval or football shaped scaffold, ora relatively unidiameter scaffold.

In some embodiments, the radially expandable element includes multipleradially deployable arms.

In some embodiments, the radially expandable element includes a radiallyexpandable tube. For example, the radially expandable tube can include atube resiliently biased in an expanded condition.

In some embodiments, the radially expandable element includes a radiallyexpandable sheet. The radially expandable sheet can include a sheetresiliently biased in an expanded condition, for example where theradially expandable sheet is configured to be furled to transition to acompact condition. The radially expandable sheet can include a sheetresiliently biased in an unexpanded condition, for example where theradially expandable sheet is configured to be unfurled to transition toan expanded condition. The radially expandable sheet can include afoldable sheet, for example a sheet configured to be folded totransition from an expanded state to an unexpanded state and configuredto be unfolded to transition from an unexpanded state to an expandedstate.

The radially expandable element can have a diameter ranging from 15 mmto 30 mm. The radially expandable element can have a length ranging from10 mm to 40 mm, such as a length ranging from 20 mm to 25 mm, or alength of less than or equal to 15 mm. In some embodiments, the radiallyexpandable element can include at least two radially expandable elementseach with a length less than or equal to 25 mm, for example less than 20mm.

The radially expandable element can be configured to be moved in amotion selected from the group consisting of: rotation; translation; andcombinations thereof. In some embodiments, the radially expandableelement can be moved manually, for example by an operator. In someembodiments, the device can include a motion transfer assemblyconfigured to move the radially expandable element. In some embodiments,the ablation element can be configured to deliver a first energydelivery and a second energy delivery, and the radially expandableelement can be configured to be moved between the first energy deliveryand the second energy delivery. In some embodiments, the ablationelement is configured to be moved during the delivery of the electricalenergy.

In some embodiments, the radially expandable element includes anexpandable helical structure. The radially expandable element canfurther include a filament comprising the ablation element and can beconfigured to be moved along the helical structure, for example where amotion transfer assembly moves the filament during the delivery ofelectrical energy.

The device can further include a second radially expandable element. Insome embodiments, the second radially expandable element can beconfigured to perform a luminal diameter measurement. In someembodiments, the second radially expandable element includes a secondablation element configured to deliver electrical energy to targettissue. In this embodiment, the first radially expandable element has afirst length, and the first radially expandable element and the secondradially expandable element are spaced apart by a distance less than orequal to the first length, for example where the second radiallyexpandable element has a second length approximately the same as thefirst radially expandable element length. In some embodiments, the firstradially expandable element has a length of less than or equal toapproximately 20 mm and the second radially expandable element has alength of less than or equal to approximately 20 mm. The device canfurther include multiple filaments extending between the first radiallyexpandable element and the second radially expandable element. In someembodiments, the multiple filaments include multiple elongate conductorsand the multiple elongate conductors include the ablation element. Insome embodiments, the ablation element includes multiple electrodesmounted to the multiple filaments. In some embodiments, the ablationelement includes a first set of electrodes positioned on the firstradially expandable element and a second set of electrodes positioned onthe second radially expandable element, for example where the first setof electrodes are configured in a first geometry and the second set ofelectrodes are configured in a second geometry different than the first,such as where the first geometry and second geometry are configured suchthat ablation with the first geometry and the second geometry causessubstantially full surface ablation of an area of tissue. In someembodiments, the second radially expandable element is positioned withinthe first radially expandable element, for example where the ablationelement includes a first set of electrodes positioned on the firstradially expandable element and a second set of electrodes positioned onthe second radially expandable element. In some embodiments, the firstradially expandable element is positioned within the second radiallyexpandable element, and the second radially expandable element includesinsulating material and a set of openings, for example where theinsulating material includes an inflatable balloon. In this embodiment,the ablation element can include a top surface area where each openingof the set of openings includes an opening area less than an electrodetop surface area.

The device can further include a second radially expandable elementdistal to the first radially expandable element and a third radiallyexpandable element distal to the second radially expandable element,where the second radially expandable element includes a second ablationelement and the third radially expandable element includes a thirdablation element. In some embodiments, the first radially expandableelement, the second radially expandable element and the third radiallyexpandable element each includes a length of less than or equal toapproximately 20 mm. In some embodiments, the first and second ablationelements are separated by a first distance and the second and thirdablation elements are separated by a second distance similar to thefirst distance. In some embodiments, the target tissue includes a set ofsequential target tissue portions comprising, in order, a first section,a second section, a third section, a fourth section, and a fifthsection, and wherein the first, second and third ablation elements areconfigured to ablate the first, third and fifth target tissue portionsin a first energy delivery and the first and second ablation elementsare configured to ablate the second and fourth target tissue portions ina second energy delivery.

The radially expandable element can be configured to be radiallycompacted to stop the delivery of the electrical energy.

The device can further include a control shaft operably coupled to theradially expandable element, where translation of the control shaftchanges the shape of the radially expandable element. For example,retraction of the control shaft causes the radially expandable elementto expand and advancement of the control shaft causes the radiallyexpandable element to expand.

The ablation element can be configured to cause non-desiccating ablationof the target tissue. The ablation element can be configured to minimizeelectrical current driven temperature increase in the outermost 50% ofthe mucosal layer, for example where the outermost 50% of the mucosallayer is ablated mainly due to thermal conduction. The ablation elementcan be configured to minimize electrical current driven temperatureincrease in the outermost 80% of the mucosal layer, for example wherethe outermost 80% of the mucosal layer is ablated mainly due to thermalconduction.

In some embodiments, at least a portion of the ablation element includesa surface area with a geometric shape comprising: a linear segment; acircle; a rectangle; and combinations of these.

In some embodiments, the ablation element includes at least a singlepair of electrodes. The single pair of electrodes can include a firstelectrode comprising multiple elongate conductors and a second electrodecomprising multiple elongate conductors. For example, the firstelectrode can include a first elongate conductor comprising a major axisthat is configured to be relatively parallel to a central axis of aportion of the small intestine (e.g. duodenum) during delivery of energywhere the first elongate conductor major axis that is configured to berelatively parallel to a central axis of a curvilinear portion of thesmall intestine (e.g. duodenum) during energy delivery. The firstelongate conductor major axis can be configured to be relativelyparallel to a central axis of a curvilinear portion of the smallintestine during energy delivery. The first electrode multiple elongateconductors can include conductors with a length of at least 10 mm, forexample at least 20 mm. The first electrode multiple elongate conductorsand the second electrode multiple elongate conductors can be positionedin an interdigitated array, for example where the interdigitatedconductors are edge-to-edge spaced at a distance less than or equal to1.5 mm, for example less than or equal to 1.0 mm or less than or equalto 750 microns. The first electrode multiple elongate conductors and thesecond elongate multiple elongate conductors can be positionedrelatively parallel to each other. The first electrode multipleconductors can include at least 4 elongate conductors.

In some embodiments, the ablation element includes at least one pair ofelectrodes. The ablation element can be configured to deliver a current,where the current passes substantially through the innermost 50% of themucosal layer, or through the innermost 20% of the mucosal layer.

In some embodiments, the ablation element includes at least oneconductor comprising a height that extends from the radially expandableelement at least 100 microns. The at least one conductor can include atissue contacting surface positioned at least 200 microns from thesurface of the radially expandable element, for example where the atleast one conductor tissue contacting surface is positioned at least 400microns from the radially expandable element. The at least one conductorcan include an electrically insulating material between the tissuecontacting surface and the radially expandable element, for examplewhere the electrically insulating material includespolytetrafluoroethylene.

In some embodiments, the ablation element includes at least 2electrodes. In some embodiments, the ablation element includes at least4 electrodes.

In some embodiments, the ablation element includes at least oneconductor with a length of approximately between 10 mm and 40 mm.

In some embodiments, the ablation element includes a first conductor anda second conductor with an edge-to-edge spacing between approximately200 microns and 2 mm.

In some embodiments, the ablation element includes at least oneconductor with a width less than or equal to 2.0 mm, for example a widthless than or equal to 1.5 mm or a width less than or equal to 1.0 mm, ora width between 400 microns and 700 microns.

In some embodiments, the ablation element includes at least oneconductor with a width greater than 230 microns.

In some embodiments, the ablation element includes at least twoconductors with a width of approximately 400 microns, for example wherethe at least two conductors with an edge to edge spacing ofapproximately 600 microns.

In some embodiments, the ablation element includes at least oneconductor with a width of approximately 700 microns, for example wherethe at least two conductors with an edge to edge spacing ofapproximately 400 microns.

In some embodiments, the ablation element includes at least oneconductor with a width less than or equal to a desired depth ofablation. In some embodiments, the ablation element includes a firstconductor and a second conductor separated by a first distance, wherethe first distance is less than or equal to a desired depth of ablation.In some embodiments, the ablation element includes an array ofconductors. For example, the array of conductors can include acircumferential array of conductors such a linear or curvilinearcircumferential array of conductors. In some embodiments, thecircumferential array of conductors comprises a helical array ofconductors. In some embodiments, the circumferential array of conductorsincludes a 360° array. In some embodiments, the circumferential array ofconductors is configured to prevent formation of a full circumferentialscar, for example where the array of conductors includes a less than350° array of conductors such as a 300° to 350° array of conductors. Insome embodiments, the circumferential array of conductors includes anarray of conductors spanning approximately 45° to 300°, for examplewhere the device is configured to be rotated to treat a 360° segment oftarget tissue. In some embodiments, the circumferential array ofconductors includes multiple pairs of conductors, for example at leastfive pairs of conductors. In some embodiments, the circumferential arrayof conductors includes conductors radially edge-to-edge spaced at adistance between approximately 230 microns and 2.0 mm, for example at adistance between approximately 400 microns to 600 microns. In someembodiments, the circumferential array of conductors includes conductorsradially spaced at a first distance, where the width of the multipleconductors is approximately half of the first distance. In someembodiments, the circumferential array of conductors includes conductorsradially spaced with a uniformity of spacing greater than or equal to95%, for example with a uniformity of spacing greater than or equal to98%.

In some embodiments, the ablation element includes an elongate copperconductor.

In some embodiments, the ablation element includes a shape selected fromthe group consisting of: a rectangle; a square; a triangle; a trapezoid;and combinations of these. The ablation element can be configured toablate tissue in a shape selected from the group consisting of: arectangle; a square; a triangle; a trapezoid; and combinations thereof.

In some embodiments, the ablation element includes multiple conductorsarranged in an operator adjustable pattern. In some embodiments, theablation element includes multiple flexible conductors.

In some embodiments, the ablation element is mounted to the radiallyexpandable element by at least one of: a glue joint; a weld; a swage ora molecular bond. In some embodiments, the ablation element is at leastpartially embedded in the radially expandable element.

The device can further include a flexible substrate, where the ablationelement is attached to the flexible substrate. The flexible substratecan include a material selected from the group consisting of: polyamide;a polyester weave; a stretchable polyurethane material; and combinationsof these. The flexible substrate can include a heat set configured toenhance folding of the flexible substrate. The ablation element caninclude multiple conductors deposited on the flexible substrate, forexample where the ablation element includes at least one conductordeposited using an ink-jet deposition process, such as where the atleast one conductor is deposited by depositing catalytic ink followed byexposure to a copper solution. The ablation element can include at leastone conductor deposited using a masked deposition process. The radiallyexpandable element can include at least three splines, where thesubstrate is attached to the at least three splines. The at least threesplines can be arranged in a symmetric circumferential pattern. The atleast three splines can form a non-circular cross section when theradially expandable element is expanded. The expandable element caninclude four splines such that when the expandable element is expanded,the substrate includes a relatively square cross section. The expandableelement can include five splines such that when the expandable elementis expanded, the substrate includes a relatively pentagonal crosssection or a relatively hexagonal cross section.

In some embodiments, the ablation element includes multiple wires.

In some embodiments, the ablation element includes multiple conductorsconfigured to rotate, for example where the multiple conductors areconfigured to rotate during the delivery of the electrical energy.

In some embodiments, the ablation element includes an anti-stickcoating, for example a polytetrafluoroethylene coating.

In some embodiments, the ablation element includes at least oneconductor configured to capacitively couple the electrical energy to thetarget tissue. The device can be configured to position the at least oneconductor such that a gap is present between the ablation element andthe target tissue. The device can further include a dielectric coveringpositioned between the at least one conductor and the target tissue, forexample where the dielectric covering comprises polytetrafluoroethylene.The dielectric covering can include a non-uniform thickness coveringincluding dielectric material, for example where the dielectric coveringincludes a middle portion with a first thickness and an edge portionwith a second thickness greater than the first thickness. The non-informthickness covering can be configured to cause uniform ablation depth ofa tissue area.

In some embodiments, the ablation element includes multiple conductorsand the device further includes multiple insulators positioned betweenthe multiple conductors. The multiple insulators can include multiplethermal conductors. Examples of insulator materials include: sapphire;fused quartz; fused silica; a polymeric material; glass; andcombinations of these.

The device can further include a second ablation element. The secondablation element can include an ablation element selected from the groupconsisting of: an RF energy delivery element such as one or moreelectrodes, each comprising one or more elongate conductors; anultrasonic transducer such as one or more piezo crystals configured toablate tissue; a laser energy delivery element such as one or moreoptical fibers and/or laser diodes; a heat delivery element such as ahot fluid filled balloon; a rotating ablation element; a circumferentialarray of ablation elements; and combinations of these.

The electrical energy delivered by the ablation element can includebipolar radiofrequency energy and/or monopolar radiofrequency energy.

In some embodiments, the elongate shaft distal portion is configured tobe at least one of deflected or steered.

The device can further include at least one sensor configured to providea signal. The device can be configured to deliver the electrical energybased on the at least one sensor signal. Examples of sensors include butare not limited to: temperature sensor; pressure sensor; impedancesensor; visual sensor; and combinations of these. The visual sensor canbe configured to provide an image of tissue, for example where thevisual sensor includes an imaging device selected from the groupconsisting of: visible light camera; infrared camera; CT Scanner; MRI;and combinations of these. The device can be configured to deliver theelectrical energy based on the visual sensor signal, for example wherethe device is configured to deliver the electrical energy based on achange in tissue color. The at least one sensor can include multipletemperature sensors, for example multiple temperature sensors positionedwith a spacing of at least 1 sensor per 1 cm². The ablation element canbe configured to deliver the electrical energy based on one or moresignals from the multiple temperature sensors. Examples of temperaturesensors include but are not limited to: thermocouple; thermistor;resistance temperature detector; optical temperature sensor; andcombinations of these. The at least one sensor can include a sensorconfigured to assess apposition of a device component with agastrointestinal wall, for example where the at least one sensorincludes a sensor configured to assess apposition of a balloon expandedto contact the gastrointestinal wall. The at least one sensor caninclude a chemical sensor, for example a carbon dioxide sensor. The atleast one sensor can be configured to assess the apposition of theradially expandable element. The device can further include a secondradially expandable element, where the at least one sensor is configuredto assess the apposition of the second radially expandable element.

The device can further include a conductive gel configured to be appliedto the target tissue, for example a gel that is at least thermally orelectrically conductive. The thermally conductive gel can be configuredto conduct heat into tissue. Alternatively or additionally, thethermally conductive gel can be configured to cool tissue, for examplewhen cool air is delivered to at least one of the gel or the tissue. Theelectrically conductive gel can be configured to improve transfer ofelectrical energy to tissue. The conductive gel can be placed on tissueand/or the ablation element prior to expansion of the radiallyexpandable element.

The device can further include an impedance monitoring assemblyconfigured to measure impedance of tissue, for example where the deviceis configured to deliver the electrical energy to the target tissuebased on the measured impedance.

According to another aspect of the present inventive concepts, a systemfor ablating tissue with electrical energy includes an ablation device,for example an ablation device as has been described hereabove, and anenergy delivery unit configured to delivery electrical energy to theablation element of the ablation device. The system can include a fluiddelivery element constructed and arranged to deliver fluid, gel or othermaterial into submucosal tissue, such as to expand the submucosaltissue. The fluid delivery element can comprise multiple fluid deliveryelements, such as one or more needles and/or one or more fluid jets. Thesystem can include one or more vacuum ports positioned proximate themultiple fluid delivery elements, such as to stabilize, manipulate orotherwise apply a force to the tissue receiving the expansion material.The submucosal tissue can be expanded to increase a target treatmentarea. The submucosal tissue can be expanded circumferentially.

The system can be configured to treat mucosal tissue of the smallintestine, such as duodenal mucosal tissue.

The system can be constructed and arranged to perform a target tissuetreatment that modifies a tissue property selected from the groupconsisting of: a secretive property of a portion of the gastrointestinaltract; an absorptive property of a portion of the gastrointestinaltract; and combinations thereof. The system can include at least onefluid delivery device constructed and arranged to deliver fluid intosubmucosal tissue to increase the volume of the target tissue.

The system delivery unit can be configured to perform a non-desiccatingablation of the target tissue.

The system can be configured to deliver energy to the target tissue withan average power density less than or equal to 20 Watts per cm², forexample an average power density less than or equal to 10 Watts per cm²or an average power density less than or equal to 4 Watts per cm². Thesystem can be configured to deliver energy to a portion of the targettissue for at least 1 second, or for at least 5 seconds, or for at least10 seconds, or for at least 20 seconds. The system can be configured todeliver energy to the target tissue at a level that decreases over time.

The system can be configured to modulate the energy delivered to thetarget tissue. For example, the system can be configured to pulse-widthmodulate the energy delivered to the target tissue where the pulse-widthmodulation comprises a cycle time, an on-time and an off-time, where theon-time is no more than 20% of the cycle time. The energy delivery unitcan include an electrical energy source less than or equal to a 300 Wattsource, for example an electrical energy source less than or equal to a150 Watt source.

The system can be configured to increase the temperature of the targettissue rapidly during energy delivery to the target tissue, for exampleat a rate of at least 17.5° C. per second. The system can be configuredto increase the temperature of the target tissue to a setpoint, wherethe setpoint temperature ranges between 60° C. and 90° C., for examplebetween 65° C. and 80° C.

The system can be configured to deliver electrical energy to a setpointtemperature, and maintain the tissue at the setpoint temperature forapproximately 2 to 40 seconds. The setpoint temperature can rangebetween 60° C. and 90° C., for example between 75° C. and 85° C., andthe tissue can be maintained at the setpoint temperature forapproximately 15 to 25 seconds.

The system can be configured to deliver electrical energy to a setpointtemperature, where one or more energy delivery parameters decay afterthe setpoint temperature is achieved. For example, the one or moreenergy delivery parameters decay at a rate configured to match aphysiological response of the tissue receiving the electrical energy.

The energy delivery unit can be configured to deliver radiofrequencyenergy to the ablation element of the ablation device, for exampleradiofrequency energy at a frequency at or below 1 MHz.

The electrical energy delivered by the ablation element can includemonopolar and/or bipolar radiofrequency energy.

The electrical energy delivered by the ablation element can include apower of less than or equal to 300 W, such as a power of approximately260 W. In one example, the power decreases from 260 W to 0 W overapproximately 30 seconds.

The energy delivery unit can deliver electrical energy to the ablationelement in a current-driven mode.

The system can be configured to deliver electrical energy to tissue andavoid desiccation of the tissue. The system can be configured to deliverelectrical energy to tissue and avoid creation of steam. The system canbe configured to deliver electrical energy to tissue and avoiddetachment of tissue particles. The system can be configured to deliverenergy in at least 2 second energy delivery durations, for example wherethe at least 2 second energy delivery durations are non-continuous.

The system can further include a second ablation device for ablatingluminal wall tissue. In some embodiments, the second ablation device issimilar to the first ablation device of the system described hereabove.In some embodiments, the second ablation device includes a radiallyexpandable element with a different expanded diameter than the firstablation device radially expandable element. In some embodiments, thefirst ablation device ablation element includes a first set of multipleconductors, and the second ablation device includes a second ablationelement comprising a second set of multiple conductors, where the firstset of multiple conductors are arranged in a different pattern than thesecond set of multiple conductors. The second ablation device caninclude an ablation device selected from the group consisting of: hotfluid filled balloon device; vapor ablation device; cryoablation device;laser ablation device; ultrasound ablation device; and combinations ofthese.

The system can further include a cooled fluid delivery device configuredto deliver fluid below 37° C. to target tissue. The cooled fluid caninclude a liquid; a gas; and combinations of these. The cooled fluiddelivery device can be configured to deliver a cooled gas toward thewall of the small intestine (e.g. duodenal wall). The cooled fluid canbe delivery prior to and/or after the delivery of the electrical energy.

The system can further include an endoscope.

The system can further include a tissue expansion device, for examplewhere the tissue expansion device includes a submucosal tissue expansiondevice configured to expand small intestine submucosal tissue (e.g.duodenal submucosal) tissue prior to the ablation element of theablation device delivering the electrical energy. The tissue expansiondevice can comprise one or more fluid delivery elements, such as one ormore needles and/or one or more water jets. The one or more fluiddelivery elements can be arranged in a linear or circumferential array.The tissue expansion device can be constructed and arranged to perform acircumferential or near circumferential expansion of tubular tissue,such as a circumferential expansion of submucosal tissue of a segment ofthe duodenum or other small intestine segment.

The system can further include an insufflation device. In someembodiments, the system further includes an endoscope having a fluiddelivery tube where the fluid delivery tube includes and/or is otherwiseconfigured as an insufflation device. The system can be configured tocontrol apposition of the ablation element with target tissue.

The system can further include a tissue cooling device. The tissuecooling device can be configured to apply cooling fluid to tissue, forexample prior and/or after the delivery of electrical energy to thetissue. The tissue cooling device can be configured to deliver a tissuecooling gas. Examples of tissue cooling gas include: air; carbondioxide; nitrogen; nitrous oxide; and combinations of these. The systemcan further include a drying assembly configured to remove moisture fromthe cooling gas prior to delivery. The tissue cooling device can providecooling fluid at a temperature less than or equal to 20° C., or examplea cooling fluid at a temperature less than or equal to 0° C.

According to another aspect of the present inventive concepts, a devicefor ablating tissue of a patient with electrical energy comprises anelongate shaft, a radially expandable element and an ablation element.The elongate shaft has a proximal portion and a distal portion. Theradially expandable element is attached to the elongate shaft distalportion. The ablation element is mounted to the radially expandableelement. The ablation element is constructed and arranged to deliverelectrical energy to target tissue. The device is constructed andarranged to modify a tissue property selected from the group consistingof: a secretive property of a portion of the gastrointestinal tract; anabsorptive property of a portion of the gastrointestinal tract; andcombinations thereof. The device can further comprise at least one fluiddelivery element constructed and arranged to deliver fluid intosubmucosal tissue to increase the volume of the target tissue. Thedevice can be constructed and arranged as described hereabove.

BRIEF DESCRIPTION OF THE DRAWINGS

The advantages of the technology described above, together with furtheradvantages, may be better understood by referring to the followingdescription taken in conjunction with the accompanying drawings. Thedrawings are not necessarily to scale, emphasis instead generally beingplaced upon illustrating the principles of the technology.

FIG. 1 is a system for ablating or otherwise treating target tissue,consistent with the present inventive concepts.

FIG. 2 is a side sectional view of the distal portion of an ablationdevice inserted into a duodenum, consistent with the present inventiveconcepts.

FIG. 2A is a magnified view of the distal portion of the ablation deviceof FIG. 2, consistent with the present inventive concepts.

FIG. 3 is a side sectional view of the distal portion of an ablationdevice inserted into a curvilinear section of duodenum, consistent withthe present inventive concepts.

FIG. 4A is perspective and magnified end views of the distal portion ofan ablation device comprising a foldable assembly, consistent with thepresent inventive concepts.

FIG. 4B is a perspective view of the ablation device of FIG. 4A, withthe foldable assembly 130 in a partially expanded state (e.g. partiallyunfolded), consistent with the present inventive concepts.

FIG. 4C is a perspective view of the ablation device of FIG. 4A, withthe foldable assembly in a fully expanded state, consistent with thepresent inventive concepts.

FIGS. 5A and 5B are side views of the distal portion of an ablationdevice comprising a helical coil, consistent with the present inventiveconcepts.

FIG. 6 is a side view of the distal portion of an ablation deviceincluding multiple expandable assemblies, consistent with the presentinventive concepts.

FIG. 7 is a side sectional view of a distal portion of an ablationdevice including an expandable assembly comprising a balloon surroundingan expandable scaffold, consistent with the present inventive concepts.

FIG. 8A is a side view of a conductor array including two electrodeseach comprising multiple elongate conductors, consistent with thepresent inventive concepts.

FIG. 8B is a side view of a conductor array including two electrodeseach comprising multiple elongate conductors, consistent with thepresent inventive concepts.

FIG. 8C is a side view of a conductor array including two electrodeseach comprising multiple elongate conductors, consistent with thepresent inventive concepts.

FIG. 8D is side and end views of an expandable assembly including ahelical array of conductors, consistent with the present inventiveconcepts.

FIG. 8E is an end view of an expandable assembly comprising threesplines and a surrounding substrate including multiple electrodes andexpanded to a triangular cross section, consistent with the presentinventive concepts.

FIG. 8F is an end view of an expandable assembly comprising four splinesand a surrounding substrate including multiple electrodes and expandedto a square cross section, consistent with the present inventiveconcepts.

FIG. 8G is an end view of an expandable assembly comprising five splinesand a surrounding substrate including multiple electrodes and expandedto a pentagonal cross section, consistent with the present inventiveconcepts.

FIGS. 9A, 9B and 9C are distal portions of three ablation devices withthree different tissue contacting portions, consistent with the presentinventive concepts.

FIG. 10 is a distal portion of an ablation device comprising multiplespline-mounted electrodes, consistent with the present inventiveconcepts.

FIG. 10A is a side sectional view of dielectric covered electrodesmounted on a spline, consistent with the present inventive concepts.

FIG. 10B is a side sectional view of an array of electrodes separated bythermal conductors, consistent with the present inventive concepts.

FIG. 10C is a top and side sectional view of an electrode with a topsurface offset from a spline, consistent with the present inventiveconcepts.

FIG. 11 is a distal portion of an ablation device including twoexpandable elements and intervening conductive filaments, consistentwith the present inventive concepts.

FIG. 12 is a distal portion of an ablation device including rotatableelectrodes, consistent with the present inventive concepts.

DETAILED DESCRIPTION OF THE DRAWINGS

Reference will now be made in detail to the present embodiments of theinventive concepts, examples of which are illustrated in theaccompanying drawings. Wherever practical, the same reference numberswill be used throughout the drawings to refer to the same or like parts.

The term “and/or” where used herein is to be taken as specificdisclosure of each of the two specified features or components with orwithout the other. For example “A and/or B” is to be taken as specificdisclosure of each of (i) A, (ii) B and (iii) A and B, just as if eachis set out individually herein.

It is an object of the present inventive concepts to provide systems,methods and devices for safely and effectively ablating a volume oftissue (the “target tissue”), such as one or more layers of a portion oftubular or solid tissue, such as tissue of an organ or tissue of thegastrointestinal tract of a patient. The systems and device of thepresent inventive concepts include one or more treatment assembliesconfigured to treat the target tissue, such as an assembly comprising aradially expandable element configured to be expanded and one or moreablation elements configured to deliver energy such as electrical energyto the target tissue. In some embodiments, the treatment elements areconstructed and arranged as described in applicant's co-pendingInternational PCT Application Serial Number PCT/US12/21739, entitled“Devices and Methods for the Treatment of Tissue”, filed Jan. 18, 2012,the contents of which is incorporated herein by reference in itsentirety.

A treatment assembly can be configured to treat target tissue in one ormore locations of the patient, such as one or more contiguous ordiscontiguous tissue locations. The target tissue comprises a threedimensional volume of tissue, and can include a first portion, atreatment portion, whose treatment has a therapeutic benefit to apatient; as well as a second portion, a “safety-margin” portion, whosetreatment has minimal or no adverse effects to the patient. Non-targettissue can be identified (e.g. prior to and/or during the medicalprocedure), wherein the non-target tissue comprises tissue whosetreatment by the treatment assembly should be reduced or avoided such asto reduce or prevent an undesired effect.

The target tissue treatment can cause one or more effects to the targettissue such as an effect selected from the group consisting of:modification of cellular function; cell death; apoptosis; instant celldeath; cell necrosis; denaturing of cells; removal of cells; andcombinations of these. In some embodiments, the target tissue treatmentis constructed and arranged to create scar tissue. Target tissue can beselected such that after treatment the treated target tissue and/ortissue that replaces the target tissue functions differently than thepre-treated target tissue, such as to have a therapeutic benefit. Themodified and/or replacement tissue can have different secretions and/orquantities of secretions than the pre-treated target tissue, such as totreat diabetes and/or obesity. The modified and/or replacement tissuecan have different absorptive properties than the target tissue, such asto treat diabetes, obesity and/or hypercholesterolemia. The effect ofthe treatment can occur acutely, such as within twenty four hours, orafter longer periods of time such as greater than twenty four hours orgreater than one week.

Target tissue to be treated can comprise two or more tissue portions,such as a first tissue portion treated with a first treatment and/or afirst treatment assembly, and a second tissue portion treated with asecond treatment and/or a second treatment assembly. The first andsecond tissue portions can be adjacent and they can contain overlappingportions of tissue. The first and second treatment and/or treatmentassemblies can be similar or dissimilar. Dissimilarities can includetype and/or amount of energy to be delivered by an energy delivery basedtreatment assembly. Other dissimilarities can include but are notlimited to: target tissue area treated; target tissue volume treated;target tissue length treated; target tissue depth treated; target tissuecircumferential portion treated; energy delivery type; energy deliveryrate and/or amount; peak energy delivered; average temperature of targettissue treatment; maximum temperature achieved during target tissuetreatment; temperature profile of target tissue treatment; duration oftarget tissue treatment; and combinations of these.

Target tissue can include tissue of the duodenum, such as tissueincluding all or a portion of the mucosal layer of the duodenum, such asto treat diabetes and/or obesity while leaving the duodenum anatomicallyconnected after treatment. Replacement tissue can comprise cells thathave migrated from one or more of: gastric mucosa; jejuna mucosa; anuntreated portion of the duodenum whose mucosal tissue functionsdifferently than the treated mucosal tissue functions prior totreatment; and combinations of these. Replacement tissue can include oneor more tissue types selected from the group consisting of: scar tissue;normal intestinal mucosa; gastric mucosa; and combinations of these. Insome embodiments, target tissue includes a treatment portion comprisingthe mucosal layer of the duodenum, and a safety-margin portioncomprising a near-full or partial layer of the submucosal layer of theduodenum. In some embodiments, the target tissue comprises nearly theentire length of the mucosal layer of the duodenum, and can include aportion of the pylorus contiguous with the duodenal mucosa and/or aportion of the jejunum contiguous with the duodenal mucosa. Treatment ofduodenal or other small intestine tissue can be performed to treat adisease and/or disorder selected from the group consisting of: diabetes;obesity; insulin resistance; a metabolic disorder and/or disease; andcombinations of these. A near full circumferential portion (e.g.approximately 360°) of the mucosal layer of one or more segments ofgastrointestinal tissue can be treated. In some embodiments, less than360° of tubular tissue is treated, such as one or more circumferentialportions less than 350°, or between 300° and 350°, such as to prevent afull circumferential scar from being created.

Target tissue can comprise tissue of the terminal ileum, such as totreat hypercholesterolemia and/or diabetes. In these embodiments, thetarget tissue can extend into the proximal ileum and/or the colon.

Target tissue can comprise gastric mucosal tissue, such as tissueregions that produce ghrelin and/or other appetite regulating hormones,such as to treat obesity and/or an appetite disorder.

Target tissue can comprise bladder wall tissue, such as to treat adisease and/or disorder selected from the group consisting of:interstitial cystitis; bladder cancer; bladder polyps; pre-cancerouslesions of the bladder; and combinations of these.

Target tissue can comprise tissue selected from the group consisting of:large and/or flat colonic polyps; margin tissue remaining after apolypectomy; and combinations of these. These tissue locations can betreated to treat residual cancer cells.

Target tissue can comprise airway lining tissue, such as to treat adisease and/or disorder selected from the group consisting of:bronchoalveolar carcinoma; other lung cancers; pre-cancerous lunglesions; and combinations of these.

Target tissue can comprise at least a portion of the intestinal tractafflicted with inflammatory bowel disease, such that Crohn's diseaseand/or ulcerative colitis can be treated.

Target tissue can comprise tissue of the oral cavity, such as to treatone or more of: oral cancers and a pre-cancerous lesion of the oralcavity.

Target tissue can comprise tissue of the nasopharynx, such as to treatnasal polyps.

Target tissue can comprise gastrointestinal tissue selected to treatCeliac disease and/or to improve intestinal barrier function.

The treatment assemblies, systems, devices and methods of the presentinventive concepts can be constructed and arranged to avoid treatingcertain tissue, termed “non-target tissue” herein. Depending on thelocation of treatment, different non-target tissue can be applicable. Incertain embodiments, non-target tissue can comprise tissue selected fromthe group consisting of: gastrointestinal adventitia; duodenaladventitia; the tunica serosa; the tunica muscularis; the outermostpartial layer of the submucosa; Ampulla of Vater such as during mucosaltreatment proximate the Ampulla of Vater; pancreas; bile duct; pylorus;and combinations of these.

As described herein, room pressure shall mean pressure of theenvironment surrounding the systems and devices of the present inventiveconcepts. Positive pressure includes pressure above room pressure or apressure that is greater than another pressure, such as a positivedifferential pressure across a fluid pathway component such as a valve.Negative pressure includes pressure below room pressure or a pressurethat is less than another pressure, such as a negative differentialpressure across a fluid component pathway such as a valve. Negativepressure can include a vacuum but does not imply a pressure below avacuum.

The treatment assemblies and expandable elements of the presentinventive concepts can be constructed and arranged to automaticallyand/or manually expand in at least a radial direction. Typicalexpandable elements include but are not limited to: an inflatableballoon; a radially expandable cage or stent; one or more radiallydeployable arms; an expandable helix; an unfurlable compacted coiledstructure; an unfurlable sheet; an unfoldable compacted structure; andcombinations of these. In some embodiments, the expandable elements cancomprise a radially expandable tube, such as a sheet of materialresiliently biased in a radially expanded condition that can becompacted through a furling operation, or a sheet of materialresiliently biased in a radially compact condition that can be expandedthrough an unfurling operation. The expandable element can comprise afoldable sheet, such as a sheet constructed and arranged to be folded tobe radially compacted and/or to be unfolded to radially expand.

Each of the expandable assemblies and treatment assemblies of thepresent inventive concepts can include one or more ablation elements,such as electrodes configured to deliver radiofrequency (RF) energy, orother functional elements such as are described in reference to thefigures herebelow. The ablation or other functional elements can bemounted on, within (e.g. within the wall) and/or inside of an expandableelement such as a balloon or expandable cage. The electrodes of thepresent inventive concepts comprise an electrically conductive element(“conductor”) configured to deliver RF energy to tissue, either throughdirect contact and/or a capacitive coupling (e.g. electrical energydelivered through a gap and/or dielectric material, such as a dielectriccovering positioned between the electrode and tissue to receiveelectrical energy from the electrode). The electrodes can comprise oneor more electrically connected segments of conductive material, such asone or more electrically connected filaments that can be arranged inparallel with one or more electrically connected filaments of a separate(electrically isolated) electrode.

The balloons of the present inventive concepts can be divided into twogeneral categories: those that are composed of a substantially elasticmaterial, such as silicone, latex, low-durometer polyurethane, and thelike; and those that are composed of a substantially inelastic material,such as polyethylene terephthalate (PET), nylon, high-durometerpolyurethane and the like. A third category includes balloons whichinclude both elastic and inelastic portions. Within the category ofelastic balloons, two subcategories exist: a first sub-category whereina combination of material properties and/or wall thickness can becombined to produce a balloon that exhibits a measurablepressure-threshold for inflation, i.e. the balloon becomes inflated onlyafter a minimum fluidic pressure is applied to the interior of theballoon; and a second sub-category, wherein the balloon expandselastically until an elastic limit is reached which effectivelyrestricts the balloon diameter to a maximum value. It will be understoodthat the individual properties of the balloons in each of thesecategories can be applied to one or more advantages in the specificembodiments disclosed herein, these properties integrated singly or incombination. By way of example only, one or more of the followingconfigurations can be employed: a highly elastic balloon can be used toachieve a wide range of operating diameters during treatment, e.g.during operation a desired balloon diameter can be achieved byadjustment of a combination of fluid temperature and pressure; asubstantially inelastic balloon or a balloon that reaches its elasticlimit within a diameter approximating a target tissue diameter (e.g. aduodenal mucosal diameter) can be used to achieve a relatively constantoperating diameter that will be substantially independent of operatingpressure and temperature; a balloon with a pressure-threshold forinflation can be used to maintain an uninflated diameter duringrelatively low pressure conditions of fluid flow and then achieve alarger operating diameter at higher pressure conditions of flow.Pressure-thresholded balloons can be configured in numerous ways. In oneembodiment, a balloon is configured to have a relatively thick wall inits uninflated state, such as to maximize an electrically and/orthermally insulating effect while the balloon is maintained in thisuninflated state. The balloon can be further configured such that itswall thickness decreases during radial expansion (e.g. to decrease anelectrically and/or thermally insulating effect). In another embodiment,a balloon is configured to have a relatively small diameter in itsuninflated state (e.g. a diameter that is small relative to the innerdiameter of tubular target tissue such as the diameter of the mucosallayer of duodenal wall tissue), such as to minimize or completelyeliminate apposition between the balloon and the surrounding tissue tominimize RF and/or other energy transfer into the surrounding tissueuntil the balloon is fully inflated. In another embodiment, a balloonand an ablation system or device are configured to circulate a flow ofhot fluid through the balloon (e.g. an elastic balloon or an inelasticballoon) at a sufficiently low enough pressure to prevent apposition ofthe balloon with target tissue, such as to pre-heat one or more surfacesof the ablation system or ablation device that are in fluidcommunication with the balloon. In this configuration, when the balloonis fully inflated, the temperature of the fluid of the balloon will beat a desired level or it will rapidly and efficiently reach the desiredlevel for treatment (i.e. minimal heat loss to the fluid path componentsdue to the pre-heating). These configurations provide a method ofdelivering energy to tissue with a hot fluid filled balloon, as well asa method of “thermal priming” prior to target tissue treatment, such asis described in applicant's co-pending U.S. Provisional Application Ser.No. 61/635,810, entitled “Tissue Expansion Devices, Systems andMethods”, filed Apr. 19, 2012, the contents of which is incorporatedherein by reference in its entirety.

Treatment Modality 1: APPOSITION BETWEEN A TREATMENT ASSEMBLY AND THETARGET TISSUE IS ESTABLISHED BY ADJUSTING THE TREATMENT ASSEMBLYDIAMETER. At times during treatment when it is desirable to increase orotherwise modify energy transfer between an ablation element such as anelectrode and the target tissue, the treatment assembly diameter (e.g.the diameter of a balloon, deployable cage, expandable tube or otherexpandable assembly) can be increased in situ so as to conform to thenative diameter of the target tissue, such as to the native diameter oftubular tissue such as small intestine wall tissue, such as duodenalwall tissue. At times during treatment when it is desirable to stop orotherwise decrease energy delivery between the treatment assembly andthe target tissue, the treatment assembly diameter can be reduced insitu, such as to prevent or reduce contact of one or more ablationelements (e.g. electrodes or hot fluid filled balloons) with the targettissue. For those cases where the native diameter of the tissue variessubstantially within the treatment zone, then a highly elastic orcompliant balloon or other expandable element can be employed, such as aballoon or deployable cage which can be adjusted to achieve a wide rangeof operating diameters.

Treatment Modality 2: APPOSITION BETWEEN THE TREATMENT ASSEMBLY AND THETARGET TISSUE IS ESTABLISHED BY CONTROLLING THE DIAMETER OF THE TARGETTISSUE. To initiate and/or increase energy delivery between a treatmentassembly and the target tissue, the diameter of the target tissue can bedecreased in situ so as to approximate and/or conform to the currentdiameter of the treatment assembly. To stop or otherwise decrease energydelivery between the treatment assembly and the target tissue, thediameter of the target tissue can be increased in situ, so as to preventor reduce contact of tissue (e.g. target tissue and/or non-targettissue) with a treatment assembly. The diameter of the tissue proximatea treatment assembly can be increased or decreased, independent of thetreatment assembly diameter, by means of delivering and/or withdrawing afluid, to and/or from a lumen surrounded by target tissue, such as byusing standard gastrointestinal insufflation techniques. Typicalinsufflation fluids include but are not limited to: gases such as carbondioxide or air; liquids such as water or saline solution; andcombinations of these. The insufflation fluids can be introduced throughthe ablation device, through an endoscope such as an endoscope throughwhich the ablation device is inserted, and/or via another device placedproximate the target tissue. Delivery of insufflation fluids can beperformed to manipulate tissue, such as to distend and/or elongatetissue. Alternatively or additionally, delivery of insufflation fluidscan be performed to move target tissue away from a treatment assembly,such as to stop transfer of energy to target tissue at the end of athermal dose period as described above. Removal of these insufflationfluids and/or the application of a vacuum or other negative pressure byone or more of the devices described hereabove, can be used to decreasethe diameter of the target tissue, such as to bring the target tissue incontact with a treatment assembly. In this tissue diameter controlledapproach, a balloon that can be maintained at a substantially constantdiameter can be desirable, such as a substantially inelastic balloonsuch as a balloon with an elastic-limit.

Referring now to FIG. 1, a system for ablating or otherwise treatingtarget tissue is illustrated, consistent with the present inventiveconcepts. System 10 is constructed and arranged to treat target tissueTT, which includes one or more tissue portions within a body lumen of amammalian patient, such as a continuous circumferential segment of aduodenum or other small intestine location. In some embodiments, targettissue TT comprises a treatment portion comprising small intestinemucosal tissue (e.g. duodenal mucosal tissue) and a safety-marginportion comprising at least an innermost layer of the small intestinesubmucosa (e.g. an innermost layer of the duodenal submucosa). System 10can be constructed and arranged to treat mucosal tissue while avoidingdamage to adventitial tissue. System 10 can include one or more ablationcatheters or other ablation devices, such as first ablation device 100and second ablation device 100′. A supply of electrical energy isprovided to at least ablation device 100 by energy delivery unit (EDU)330, typically a supply of radiofrequency (RF) energy. A device fordelivering fluid, fluid delivery unit 340, can be included in system 10,such as to deliver one or more fluids (e.g. one or more cooling and/orwarming fluids) to modify the temperature of tissue and/or modify thetemperature of one or more system device components. A controllinginterface, controller 360 can be operably attached to one or morecomponents of system 10, such as EDU 330, fluid delivery unit 340 and/oranother device or assembly of system 10, such as to control and/ormonitor one or more parameters of the attached device or assembly.

In the embodiment of FIG. 1, ablation device 100 includes coaxial shafts111 a and 111 b. Shaft 111 b has a distal end 112. Shafts 111 a and 111b are sized and configured such that shaft 111 a slidingly receivesshaft 111 b, such that they can be advanced and/or retracted in unisonor independently. In some embodiments, device 100 comprises a flexibleportion (e.g. a portion of shafts 111 a and 111 b including distal end112) with a diameter less than 6 mm. In some embodiments, the flexibleportion comprises a diameter less than 4.2 mm, less than 3.8 mm, lessthan 3.2 mm or less than 2.8 mm, such as to be slidingly received by aworking channel of an endoscope that accepts diameters less than 6 mm.In some embodiments, device 100 comprises a shaft length of 100 cm orlonger, or otherwise comprises a length sufficient to be orally and/ornasally inserted to reach the esophagus, stomach, duodenum, jejunum orterminal ileum of a patient. In FIG. 1, shafts 111 a and 111 b have beeninserted through a working channel (e.g. a 6 mm working channel), lumen351, of endoscope 350, typically a gastrointestinal endoscope. Shafts111 a and/or 111 b can be inserted over a standard interventionalguidewire, such as guidewire 371 shown exiting distal end 112 of shaft111 b. In an alternative embodiment, shafts 111 a and 111 b arepositioned in a side-by-side configuration, such as to be placed in twoseparate lumens of endoscope 350 or in two other non-coaxial locations.In some embodiments, one or both of shafts 111 a or 111 b can beinserted alongside endoscope 350 (i.e. not through lumen 351, travelingparallel with but external to endoscope 350). Shaft 111 a and 111 b caninclude deflection means constructed and arranged to steer a distalportion of the shaft, such as is described in reference to FIGS. 9A-9Cherebelow.

Ablation device 100 further includes two radially expandable assemblies,expandable assembly 130 a, and expandable assembly 130 b, mounted toshafts 111 a and 111 b, respectively. Expandable assemblies 130 a and130 b can be constructed and arranged in one or more various forms totreat, modify, measure and/or diagnose target tissue TT and/or othertubular tissue. Expandable assemblies 130 a and 130 b can comprise anexpandable element selected from the group consisting of: an inflatableballoon; a radially expandable stent or cage; an array of splines; oneor more radially deployable arms; a spiral or other helical structure; afurlable structure such as a furlable sheet; an unfurlable structuresuch as an unfurlable sheet; a foldable structure such as a foldablesheet; an unfoldable structure such as an unfoldable sheet; andcombinations of these. Expandable assembly 130 a can be positionedproximal to expandable assembly 130 b as shown in FIG. 1, oralternatively, expandable assembly 130 b can be positioned proximal toexpandable assembly 130 a, such as when expandable assembly 130 a ismounted to shaft 111 b and expandable assembly 130 b is mounted to shaft111 a.

In some embodiments, expandable assembly 130 a and/or 130 b comprise alength of at least 10 mm, such as a length between 10 mm and 40 mm, alength between 15 mm and 30 mm, or a length between 20 mm and 25 mm. Insome embodiments, expandable assembly 130 a and/or 130 b comprise alength less than or equal to 15 mm, such as when configured to treatcurvilinear portions of the gastrointestinal tract. Multiple expandableassemblies (e.g. between two and twenty expandable assemblies), such asexpandable assemblies 130 a and 130 b, can be separated along a shaft bya distance less than or equal to 25 mm, such as a distance less than orequal to 20 mm. In some embodiments, expandable assembly 130 a comprisesa length, and the separation distance between expandable assembly 130 aand 130 b is less than or equal to the expandable assembly 130 a length.In these embodiments, expandable assembly 130 b can comprise a similarlength to that of expandable assembly 130 a, such as when bothexpandable assembly 130 a and expandable assembly 130 b compriseablation elements.

Expandable assembly 130 a and/or 130 b can be constructed and arrangedto expand to a diameter of at least 15 mm, such as a diameter of atleast 20 mm, 25 mm or at least 30 mm. Expandable assembly 130 a and/or130 b can be resiliently biased, such as in a radially expanded orradially compacted state. Expandable assembly 130 a and/or 130 b can beexpanded and/or compacted by a control shaft, not shown but described indetail in reference to FIG. 10 herebelow. Expandable assembly 130 aand/or 130 b can be constructed and arranged to achieve a round ornon-round shape (e.g. an oval or football shape) when expanded.Expandable assembly 130 a and/or 130 b can approximate a tube shape whenexpanded, such as a unidiameter or varying diameter tube shape. A tissuecontacting portion of expandable assembly 130 a and/or 130 b cancomprise a shape selected from the group consisting of: triangle;rectangle; pentagon; hexagon; trapezoid; and combinations of these,examples of which are described in reference to FIGS. 9A-9C herebelow.Expandable assembly 130 a and/or 130 b can be constructed and arrangedto unfold to a radially expanded state, or to fold to a radiallycompacted state, such as is described in reference to FIG. 4A-4Cherebelow.

Expandable assembly 130 a can comprise at least one functional element131 a, and expandable assembly 130 b can comprise at least onefunctional element 131 b. Functional elements 131 a and/or 131 b can beelements selected from the group consisting of: an ablation element suchas one or more electrodes constructed and arranged to deliver electricalenergy such as radiofrequency (RF) energy; a sensor; a transducer; afluid delivery element such as a needle, a fluid jet, a permeablemembrane and/or an exit port; and combinations of these.

In some embodiments, expandable assembly 130 a is constructed andarranged to ablate tissue, and expandable assembly 130 b is constructedand arranged to perform at least one non-ablative function. Expandableassembly 130 b can be constructed and arranged to occlude or partiallyocclude a lumen surrounded by tissue, such as a lumen of thegastrointestinal tract to be occluded during an insufflation procedure.Expandable assembly 130 b can be constructed and arranged to manipulatetissue, such as to linearize and/or distend gastrointestinal tissue byfrictionally engaging (e.g. when expanded) and applying forces to thetissue (e.g. by advancing and/or retracting shaft 111 b). Expandableassembly 130 b can be constructed and arranged to test and/or diagnosetissue, such as when expandable assembly 130 b is used to measure adiameter of tubular tissue into which it has been inserted. Diametermeasurements can be performed in various ways, including but not limitedto: injection of a radiopaque fluid into assembly 130 b and fluoroscopicmeasurement of the injected fluid; controlled inflation of assembly 130b to a pressure whose level corresponds to a luminal diameter; andcombinations of these. In some embodiments, system 10 includes aseparate device, such as a balloon catheter, used to perform a diametermeasurement. One or more energy delivery parameters can be adjustedbased on the measured diameter of target tissue and/or a target tissueportion.

In some embodiments, expandable assembly 130 b is constructed andarranged to expand or otherwise modify one or more layers of tissue,such as to when functional element 131 b comprises one or more needlesand/or one or more water jets constructed and arranged to expandsubmucosal tissue of the gastrointestinal tract. Alternatively oradditionally, system 10 can include a separate tissue expansion device,tissue expansion device 390. Expandable assembly 130 b and/or tissueexpansion device 390 can be constructed and arranged as is described inapplicant's co-pending International Application Serial NumberPCT/US2013/37485, entitled “Tissue Expansion Devices, Systems andMethods”, filed Apr. 19, 2013, the contents of which is incorporatedherein by reference in its entirety. Expandable assembly 130 b and/ortissue expansion device 390 can include single or multiple fluiddelivery elements, such as one or more needles and/or one or more waterjets configured to deliver a fluid, gel or other material into tissue.Tissue expansion device 390 includes fluid delivery element 391, whichcan be attached to a radially expandable assembly, such as expandableassembly 393. Expandable assembly 393 can comprise an expandableballoon. Alternatively or additionally, expandable assembly 130 b caninclude a fluid delivery element, such as fluid delivery element 129 asshown. Fluid delivery elements 391 and/or 129 can be attached to one ormore fluid delivery tubes, not shown but attachable to a source offluid. Fluid delivery elements 391 and/or 129 can be constructed andarranged to cause a circumferential expansion of tissue, such as acircumferential expansion of submucosal tissue of the duodenum or othersmall intestine location. Fluid delivery elements 391 and/or 129 cancomprise an array of fluid delivery elements, such as a circumferentialor linear array of needles and/or water jets. A vacuum can be appliedproximate fluid delivery elements 391 and/or 129 to stabilize,manipulate or otherwise apply a force to the tissue receiving theexpansion material. A vacuum can be applied via a port proximate thefluid delivery element, such as vacuum port 392 positioned proximatefluid delivery element 391. Tissue expansion can greatly alleviate theneed for precision of treatment, such as precision of energy delivery,due to the increased size (e.g. increased depth) of the target tissueincluding an associated safety-margin of tissue to which treatmentcauses no significant adverse event (e.g. an expanded submucosal layerprior to a mucosal layer ablation). Treatment of target tissue aftersubmucosal expansion is described in reference to FIG. 2 herebelow.

Expandable assembly 130 a of FIG. 1 includes an ablation elementcomprising a pair of electrodes, first electrode 136 a and secondelectrode 137 a. In some embodiments, three or more electrodes can beincluded, such as an expandable assembly 130 a which includes at least 4electrodes. Electrodes 136 a and/or 137 a can be mounted on, withinand/or inside of expandable assembly 130 a. Electrodes 136 a and/or 137a can be positioned to directly contact tissue for RF energy delivery,or they can be separated by a gap and/or dielectric material allowingcapacitive coupling transfer of RF energy to tissue.

Electrodes 136 a and/or 137 a can comprise multiple elongate conductors,such as multiple elongate copper conductors in the interdigitated,parallel arrangement shown in FIG. 1. Electrodes 136 a and/or 137 a cancomprise flexible conductors, such as flexible copper conductors thatflex as expandable assembly 130 a transitions between radially compactedand radially expanded conditions. Electrodes 136 a and 137 a can beattached to expandable assembly 130 a with one or more attachmentelements such as at least one of: a glue joint; a weld; a swage or amolecular bond. Electrodes 136 a and 137 a can be at least partiallyembedded in a portion of expandable assembly 130 a, such as within thewall of a balloon when expandable assembly 130 a comprises an inflatableballoon. Expandable assembly 130 a can comprise a flexible substrate towhich electrodes 136 a and 137 a are attached, such as the flexiblesubstrate described in reference to FIG. 8A herebelow. Electrodes 136 aand/or 137 a can comprise a wire construction, such as a copper and/orother conductive wire with a diameter less then 500 microns. Electrodes136 a and/or 137 a can include one or more anti-stick coatings and/orcoverings, such as a coating and/or covering includingpolytetrafluoroethylene.

In some embodiments, expandable assemblies 130 a and/or 130 b comprise ashape that can be adjusted by an operator, such as via a control rod asis described in reference to FIG. and 10 herebelow. In some embodiments,the shape of the arrangement of electrodes 136 a and/or 137 a (e.g.arrangement between two separate electrodes and/or arrangement ofconductors within a single electrode) can be operator modified byadjusting the shape of expandable assembly 130 a.

Electrodes 136 a and 137 a can comprise capacitively coupled electrodes,such as those described in reference to FIG. 10A herebelow. Electrodes136 a and/or 137 a can be constructed and arranged to transfer RF energyto the target tissue via a capacitive coupling including a gap and/ordielectric material between the electrode and the target tissue. Adielectric sheet or other covering can be included, with uniform ornon-inform thickness. In some embodiments, a non-uniform thicknesscomprising thicker edge portions than middle portions can be included,such as to tend to create a uniform ablation depth (e.g. minimizingundesired edge effects along an electrodes perimeter).

Electrode 136 a is electrically attached to wire 138 a and electrode 137a is electrically attached to wire 139 a. Wires 138 a and 139 a travelproximally within shaft 111 b and are electrically attached to EDU 330,via one or more connections such as one or more operator attachableplugs and/or other electromechanical connections. System 10 can includeground pad 332, such as a standard RF energy delivery ground padtypically placed on the patient's back, such that EDU 330 can supply RFenergy to electrodes 136 a, 137 a and/or any other electrodes of system10 in monopolar, bipolar and/or combined monopolar-bipolar modes.Electrodes 136 a and/or 137 a can be configured to ablate variousthickness of gastrointestinal tissue, such as at least the innermost 500microns of small intestine tissue (e.g. at least the innermost 500microns of duodenal tissue). Electrodes 136 a and 137 a can beconfigured to ablate a volume of tissue comprising a surface area and adepth, where the ratio of depth to surface area is less than or equal to1 to 100 (e.g. less than 1%), or less than or equal to 1 to 1000 (e.g.less than 0.1%). In some embodiments, expandable assemblies 130 a and/or130 b are constructed and arranged to be in a relatively rigid state,such as during delivery of electrical energy to target tissue TT. Therigidity can be used to maintain a pre-determined spacing of one or moreconductors delivering RF energy, such as the spacing between parallel,neighboring conductors of electrodes 136 a and 137 a.

Electrodes 136 a, 137 a and/or other ablation elements of the presentinventive concepts can include copper and/or other conductive materialsarranged in various patterns, such that EDU 330 can deliver bipolarenergy in associated patterns. Bipolar RF energy can be deliveredbetween a first elongate conductor (e.g. of electrode 136 a) and asecond elongate conductor (e.g. of electrode 137 a), such as twofilaments positioned directly next to each other, or two filamentsseparated by one or more other conductors (e.g. separated by a conductorelectrically isolated from the two filaments receiving the bipolar RFenergy current delivered by EDU 330). In some embodiments, electricalenergy is delivered between two elongate conductors, such as the pairsof conductors of electrodes 136 a and 137 a shown, where the spacingbetween the edges of two neighboring conductors of electrodes 136 a and137 a (hereinafter the “edge-to-edge spacing” as illustrated in FIG. 2A)is between 200 micron and 2 mm. In some embodiments, the edge-to-edgespacing is less than or equal to 1.5 mm, such as less than 1.0 mm orless than 750 microns.

Electrodes 136 a, 137 a and/or other ablation elements of the presentinventive concepts can comprise one or more elongate conductors with awidth less than 2.0 mm, such as a width less than 1.5 mm, less than 1.0mm or between 400 and 700 microns. In some embodiments, at least oneelectrode comprises one or more elongate conductors with a width of atleast 230 microns. In some embodiments, at least one electrode comprisesan elongate conductor with a width of at least 400 microns, such as apair of electrodes comprising a pair of conductors with an edge-to-edgespacing of approximately 600 microns. In some embodiments, at least oneelectrode comprises an elongate conductor with a width of at least 700microns, such as a pair of electrodes comprising a pair of conductorswith an edge-to-edge spacing of approximately 400 microns. In someembodiments, at least one electrode comprises an elongate conductor witha width whose value is less than or equal to a desired depth ofablation. In some embodiments, a first electrode comprises a firstconductor, and a second electrode comprises a second conductor, and thefirst conductor and the second conductor (hereinafter a “conductor pair”as illustrated in FIG. 2A) have an edge-to-edge spacing that is lessthan or equal to the desired depth of ablation. In some embodiments,conductor pairs have an edge-to-edge spacing between 230 microns and 2.0mm, such as a spacing between 400 microns and 600 microns. In someembodiments, at least one conductor of a conductor pair has a widthapproximately 50% of the edge-to-edge spacing of that conductor pair. Insome embodiments, multiple conductor pairs have similar edge-to-edgespacing, such as an edge to edge spacing with a uniformity greater thanor equal to 95%, or greater than or equal to 98%.

Electrodes 136 a, 137 a and/or other ablation elements of the presentinventive concepts can be arranged in an array of electrically connectedor electrically isolated conductors, such as a circumferential array oflinear and/or curvilinear elongate conductors. The circumferential arraycan comprise a partial circumferential array of conductors (e.g. as isshown in FIG. 1) such as an array covering approximately 45° to 300° ofcircumferential area. Partial circumferential arrays of conductors cantreat a first target tissue portion and a second target tissue portionin two sequential steps, wherein the array is rotated between energydeliveries. Alternatively, the circumferential array can comprise a full360° array of conductors (e.g. a full 360° array of interdigitated pairsof conductors comprising a single or multiple pairs of electrodes), suchthat a full circumferential volume of target tissue can be treated in asingle energy delivery or in multiple energy deliveries that do notrequire repositioning of ablation device 100. In some embodiments, thecircumferential array can be constructed and arranged to avoid creationof a full circumferential scar in tubular tissue, such as an array ofbetween 300° and 350° of one or more electrodes (e.g. a 300° to 350°array of interdigitated pairs of conductors comprising a single ormultiple pairs of electrodes). Two or more electrodes can be arranged ina helical array of two or more conductors. Two or more pairs of singleor multiple filament conductors can be included, with any combination orarrangement of pairs driven by bipolar RF energy to treat the targettissue. In some embodiments, at least three, four or five pairs ofconductors are driven simultaneously or sequentially by bipolar RFenergy to treat the target tissue.

Electrodes 136 a, 137 a and/or other ablation elements of the presentinventive concepts can comprise a sufficient length (singly or incombination) to treat substantially the entire length of the targettissue simultaneously or at least without having to reposition ablationdevice 100. In some embodiments, the target tissue comprisessubstantially the entire length of the duodenum. Electrodes 136 a, 137 aand/or other ablation elements of the present inventive concepts cancomprise a sufficient length (singly or in combination) to treat atleast 50% of the entire length of the target tissue simultaneously or atleast without having to reposition ablation device 100. In someembodiments, the target tissue comprises at least 50% of the length ofthe duodenum. Electrodes 136 a, 137 a and/or other ablation elements ofthe present inventive concepts can be constructed and arranged to treata first portion of target tissue followed by a second portion of targetissue. The first and second treated tissue portions can be overlappingand they can have non-parallel central axes (e.g. tissue portions in acurved portion of the duodenum or other small intestine location). Threeor more target tissue portions can be treated, such as to cumulativelyablate at least 50% of the duodenal mucosa.

In some embodiments, functional element 131 b of expandable assembly 130b comprises one or more electrical energy delivery or non-electricalenergy delivery ablation elements, such as those described inapplicant's co-pending International PCT Application Serial NumberPCT/US12/21739, entitled “Devices and Methods for the Treatment ofTissue”, filed Jan. 18, 2012, the contents of which is incorporatedherein by reference in its entirety. In some embodiments, functionalelement 131 b comprises an ablation element selected from the groupconsisting of: an RF energy delivery element such as one or moreelectrodes, each comprising one or more elongate conductors; anultrasonic transducer such as one or more piezo crystals configured toablate tissue; a laser energy delivery element such as one or moreoptical fibers and/or laser diodes; a heat delivery element such as ahot fluid filled balloon; a rotating ablation element; a circumferentialarray of ablation elements; and combinations of these. In theseembodiments, either or both expandable assembly 130 a and 130 b can beused to ablate target tissue TT.

In some embodiments, expandable assemblies 130 a and/or 130 b compriseinflatable or otherwise expandable balloons, such as one or more of: acompliant balloon; a non-compliant balloon; a balloon with a pressurethreshold; a balloon with compliant and non-compliant portions; aballoon with a fluid entry port; a balloon with a fluid exit port; andcombinations of these. In some embodiments, expandable assemblies 130 aand/or 130 b comprise a balloon which is fluidly attached to aninflation tube, such as an inflation tube which travels proximallythrough shaft 111 a and/or 111 b and is attached to an inflation port,not shown but typically attached to a handle on the proximal end ofablation device 100.

In some embodiments, expandable assembly 130 b comprises an abrasiveelement configured for abrading target tissue, such as an abrasiveelement attached to a balloon or expandable cage.

Shafts 111 a and 111 b can include one or more lumens passingtherethrough, and can comprise wires and/or optical fibers for transferof data and/or energy such as RF energy to electrodes 136 a and 137 a ofassembly 130 a. Shafts 111 a and/or 111 b can comprise one or moreshafts, such as one or more concentric shafts configured to deliverand/or re-circulate hot and/or cold fluid through expandable assemblies130 a and/or 130 b, respectively, such as to deliver a bolus of hotfluid energy and/or other thermal dose as described in applicant'sco-pending International Application Serial Number PCT/US2013/28082,entitled “Heat Ablation Systems, Devices and Methods for the Treatmentof Tissue”, filed Feb. 27, 2013, the contents of which is incorporatedherein by reference in its entirety. Device 100 can comprise a singleexpandable assembly 130 a, without inclusion of expandable assembly 130b, as is described in reference to multiple embodiments herebelow.

Expandable assembly 130 a and/or 130 b can be constructed and arrangedto ablate tissue or otherwise perform a function while positioned in acurved segment of the gastrointestinal tract, such as is described inreference to FIG. 3 herebelow.

The systems of the prevent inventive concepts are constructed andarranged to ablate or otherwise treat target tissue TT, such as duodenalor other small intestinal mucosal tissue, while avoiding damagingnon-target tissue, such as the gastrointestinal adventitia. Targettissue TT can include at least a portion of safety-margin tissuecomprising tissue whose ablation causes minimal or no adverse effect tothe patient, such as sub-mucosal tissue of the gastrointestinal tract.Target tissue TT can comprise one or more portions of tissue that aretreated simultaneously or sequentially. In some embodiments, the targettissue TT comprises the majority of the length of the duodenal mucosa,such as at least 50% of the duodenal mucosa. In some embodiments, thetarget tissue TT comprises at least 90% of the duodenal mucosa, or atleast 95% of the duodenal mucosa. In some embodiments, the target tissueTT includes the full mucosal thickness of at least a portion of duodenalor other small intestinal tissue, as well as at least the innermost 100microns of submucosal tissue, or at least the innermost 200 microns ofsubmucosal tissue. In some embodiments, system 10 and/or ablation device100 is constructed and arranged to avoid ablating at least an outermostlayer of small intestine submucosal tissue (e.g. avoid ablating anoutermost layer of duodenal submucosal tissue), such as a non-ablatedoutermost layer that is at least 100 microns thick, or at least 200microns thick. The target tissue TT can include at least one of ilealmucosal tissue or gastric mucosal tissue.

Endoscope 350 can be a standard endoscope, such as a standardgastrointestinal endoscope, or a customized endoscope, such as anendoscope including sensor 353 configured to provide information relatedto the tissue treatment of the present inventive concepts. Endoscope 350can include camera 352, such as a visible light, ultrasound and/or othervisualization device used by the operator of system 10 prior to, duringand/or after the treatment of target tissue TT, such as during insertionand/or removal of endoscope 350 and/or shafts 111 a and 111 b ofablation device 100. Camera 352 can provide direct visualization ofinternal body spaces and tissue, such as the internal organs of thegastrointestinal tract. Endoscope 350 can be coupled with or otherwiseinclude a guidewire, e.g. guidewire 371, such as to allow insertion ofendoscope 350 into the jejunum.

System 10 can be constructed and arranged to perform insufflation of abody lumen, such as a segment of the gastrointestinal tract. The bodylumen can be pressurized, such as by using one or more standardinsufflation techniques. Insufflation fluid can be introduced throughsecond lumen 354 of endoscope 350. Second lumen 354 travels proximallyand connects to a source of insufflation liquid and/or gas, such asfluid delivery unit 340, and typically a source of air, carbon dioxide,water and/or saline. Alternatively or additionally, insufflation fluidcan be delivered by ablation device 100, such as through shaft 111 aand/or 111 b, and/or through a port in expandable assembly 130 a and/or130 b, such as when functional elements 131 a and/or 131 b,respectively, comprise a fluid delivery port attached to a source ofinsufflation liquid and/or gas. Alternatively or additionally, aseparate device configured to be inserted through endoscope 350 and/orto be positioned alongside endoscope 350, can have one or more lumensconfigured to deliver the insufflation fluid. System 10 can include oneor more occlusive elements and/or devices, such as expandable assemblies130 a, 130 b and/or another expandable device configured to radiallyexpand such as to fully or partially occlude a body lumen, such thatinsufflation pressure can be achieved and/or maintained over time (e.g.reduce or prevent undesired migration of insufflation fluid). The one ormore occlusive elements and/or devices can be positioned proximal toand/or distal to the luminal segment to be insufflated.

Functional element 131 a and/or functional element 131 b can comprise asensor. In some embodiments, functional element 131 a, functionalelement 131 b, sensor 353 and/or another sensor of system 10 cancomprise a sensor selected from the group consisting of: temperaturesensors such as thermocouples, thermistors, resistance temperaturedetectors and optical temperature sensors; strain gauges; impedancesensors such as tissue impedance sensors; pressure sensors; bloodsensors; optical sensors such as light sensors; sound sensors such asultrasound sensors; electromagnetic sensors such as electromagneticfield sensors; and combinations of these. The sensors can be configuredto provide information to one or more components of system 10, such asto controller 360 and/or EDU 330, such as to monitor the treatment oftarget tissue TT and/or to treat target tissue TT in a closed loopconfiguration. Energy delivery from EDU 330 can be modified based on oneor more sensor readings. In one embodiment, an algorithm of controller360 and/or EDU 330 processes one or more sensor signals to modify amountof energy delivered, power of energy delivered, voltage of energydelivered, current of energy delivered and/or temperature of energydelivery.

A sensor such as a chemical detection sensor can be included, such as toconfirm proper apposition of expandable assemblies 130 a and/or 130 b.In this configuration, a chemical sensor such as a carbon dioxide sensorcan be placed distal to expandable assemblies 130 a and/or 130 b, and afluid such as carbon dioxide gas is introduced proximal to theexpandable assemblies 130 a and/or 130 b. Detection of the introducedfluid can indicate inadequate apposition of expandable assemblies 130 aand/or 130 b, such as to prevent inadequate transfer of energy to targettissue TT and/or prevent inadequate measurement, modification and/ordiagnosis of target tissue TT.

Functional element 131 a, functional element 131 b, sensor 353 and/oranother sensor of system 10 can comprise a sensor configured to provideinformation related to the tissue treatment performed by expandableassembly 130 a and/or 130 b, such as a visual sensor mounted toexpandable assembly 130 a that is configured to differentiate tissuetypes that are proximate expandable assembly 130 a, such as todifferentiate mucosal and submucosal tissue. Applicable visible sensorsinclude but are not limited to: visible light camera; infrared camera;CT Scanner; MRI; and combinations of these. In some embodiments,electrical energy delivered by electrodes 136 a, 137 a and/or otherablation elements of system 10 is based on one or more signals from thevisible sensor, such as a sensor providing a signal correlating totissue color. Functional elements 131 a and 131 b can comprise a sensorconfigured to provide information related to the tissue treatmentperformed by expandable assembly 130 a and/or 130 b, such as atemperature sensor configured to monitor the temperature of treatmentprovided by expandable assembly 130 a and/or tissue proximate expandableassembly 130 a. Functional elements 131 a and/or 131 b can comprisemultiple temperature sensors, such as multiple temperature sensorspositioned on expandable assembly 130 a and/or 130 b, respectively, witha spacing of at least one sensor per square centimeter. RF and/or otherenergy delivered by EDU 330 can be based on signals recorded by themultiple temperature sensors.

Functional element 131 a and/or functional element 131 b can comprise atransducer. In these and other embodiments, functional element 131 a,functional element 131 b, and/or another transducer of system 10 can bea transducer selected from the group consisting of: a heat generatingelement; a drug delivery element such as an iontophoretic drug deliveryelement; a magnetic field generator; an ultrasound wave generator suchas a piezo crystal; a light producing element such as a visible and/orinfrared light emitting diode; and combinations of these.

EDU 330 is configured to deliver energy to one or more ablation elementsof system 10. In some embodiments, EDU 330 is configured to deliver atleast RF energy, and system 10 includes ground pad 332 configured to beattached to the patient (e.g. on the back of the patient), such that RFenergy can be delivered in monopolar delivery mode to electrode 136 a,137 a and/or another electrode of system 10. Alternatively oradditionally, EDU 330 can be configured to deliver energy in a bipolarRF mode, such as bipolar energy delivered between electrodes 136 a and137 a of expandable assembly 130 a. Alternatively or additionally, EDU330 can be configured to deliver energy in a combined monopolar-bipolarmode.

EDU 330 can be constructed and arranged to deliver RF and/or other formsof energy to one or more ablation elements of expandable assembly 130 aand/or 130 b. In some embodiments, EDU 330 delivers energy selected fromthe group consisting of: RF energy; microwave energy; plasma energy;ultrasound energy; light energy; and combinations of these. Energy canbe continuous and/or pulsed, and can be delivered in a closed-loopfashion as described hereabove. Energy delivery parameters such aspower, voltage, current and frequency can be held relatively constant orthey can be varied by EDU 330. Energy delivery can be varied from afirst tissue location (e.g. a first portion of target tissue) to asecond location (e.g. a second portion of target tissue), such as adecrease in energy from a first treated location to a second treatedlocation when the second treated location is thinner than the firsttreated location. Alternatively or additionally, energy delivery can bevaried during a single application of energy to a single tissuelocation, such as by adjusting one or more energy delivery parametersduring a continuous energy delivery.

System 10 can be further configured to deliver and extract one or morefluids from expandable assembly 130 a and/or 130 b, such as to pre-heatexpandable assembly 130 a and/or 130 b and/or to deliver heat energy totarget tissue TT via the delivered fluids. In one embodiment, fluiddelivery unit 340 and/or EDU 330 are configured to deliver one or moresupplies of hot fluid, such as hot water or saline when expandableassembly 130 a and/or 130 b comprises a balloon positioned at the end ofone or more fluid delivery tubes, not shown but typically as describedin applicant's co-pending International Application Serial NumberPCT/US2013/28082, entitled “Heat Ablation Systems, Devices and Methodsfor the Treatment of Tissue”, filed Feb. 27, 2013, the contents of whichis incorporated herein by reference in its entirety. In theseembodiments, fluid delivery unit 340 and/or EDU 330 typically includesone or more fluid pumps, such as one or more peristaltic, displacementand/or other fluid pumps; as well as one or more heat exchangers and/orother fluid heating elements internal and/or external to device 100.Fluid delivery unit 340 and/or EDU 330 can be constructed and arrangedto rapidly deliver and/or withdraw fluid to and/or from expandableassemblies 130 a and/or 130 b via one or more fluid transport means.Fluid transport means can include a pump configured to deliver fluid ata flow rate of at least 50 ml/min and/or a pump and/or vacuum sourceconfigured to remove fluid at a flow rate of at least 50 ml/min. A pumpand/or vacuum source can be configured to continuously exchange hotfluid and/or to perform a negative pressure priming event to removefluid from one or more fluid pathways of device 100. Fluid delivery unit340, EDU 330 and/or ablation device 100 can include one or more valvesin the fluid delivery and/or fluid withdrawal pathways or one or moreother valves in the fluid pathway within expandable assemblies 130 aand/or 130 b. Valves can be configured to control entry of fluid into anarea and/or to maintain pressure of fluid within an area. Valves can beused to transition from a heating fluid, such as a fluid of 90° C.maintained in a treatment assembly for approximately 12 seconds, to acooling fluid, such as a fluid between 4° C. and 10° C. maintained inthe assembly element for approximately 30 to 60 seconds. Typical valvesinclude but are not limited to: duck-bill valves; slit valves;electronically activated valves; pressure relief valves; andcombinations of these. Fluid delivery unit 340 and/or EDU 330 can beconfigured to rapidly inflate and/or deflate expandable assemblies 130 aand/or 130 b. Fluid delivery unit 340 and/or EDU 330 can be configuredto purge the fluid pathways of device 100 with a gas such as air, suchas to remove cold and/or hot fluid from device 100 and/or to remove gasbubbles from device 100.

System 10 can include conductive gel 333, constructed and arranged toconduct thermal and/or electrical energy between a component of system10 and tissue. Conductive gel 333 can be delivered by ablation device100, such as via a port in expandable assembly 130 a and/or 130 b, notshown but typically connected to a fluid delivery tube that travelsproximally to a handle on device 100, and/or via another device ofsystem 10. Conductive gel 333 can be delivered to at least one of tissueor an external surface of a portion of a device of system 10, such asthe external surface of expandable assembly 130 a and/or 130 b.Conductive gel 333 can be thermally conductive such as to improve heattransfer to tissue. Conductive gel 333 can be thermally conductive suchas to improve cooling of tissue, such as when cool air is delivered togel 333 and/or tissue via a component of system 10. Conductive gel 333can be electrically conductive to improve transfer of electrical energyto tissue. System 10 can be constructed and arranged to allow anoperator to place conductive gel 333 onto tissue prior to expansion ofexpandable assembly 130 a and/or 130 b. System 10 can be constructed andarranged to allow an operator to place conductive gel 333 onto electrode136 a and/or 137 a prior to electrode 136 a and/or 137 a, respectively,contacting target tissue and/or delivering RF energy to tissue.

EDU 330, electrodes 136 a and 137 a and/or other components of system 10can be constructed and arranged to treat target tissue TT with anon-desiccating ablation, such as by avoiding tissue temperatures above100° C., avoiding the creation of steam, or otherwise avoidingdeleterious desiccation of tissue. System 10 can be constructed andarranged to minimize heat production in the outermost 50% of a mucosallayer (e.g. to minimize RF current flow in the outermost 50% of amucosal layer). In these embodiments, the outermost 50% of the mucosallayer can be ablated via thermal conduction (e.g. thermal conductionfrom the innermost 50% of the mucosal layer). Similarly, system 10 canbe constructed and arranged to minimize heat production in the outermost80% of a mucosal layer, such as to ablate the outermost 80% of themucosal layer via thermal conduction. System 10 can be constructed andarranged to maximize the flow of current, such as through the innermost50% of a mucosal layer, or through the innermost 20% of a mucosal layer.In some embodiments, system 10 can be constructed and arranged to avoiddetachment of tissue particles.

EDU 330, electrodes 136 a and 137 a and/or other components of system 10can be constructed and arranged to deliver RF energy to target tissue ata power density that averages less than 20 watts per cm², such as apower density that averages less than 10 watts per cm² or less than 4watts per cm². RF energy can be delivered for a particular portion oftarget tissue for a time period of at least one second, such as a timeperiod of at least 5 seconds, at least 10 seconds or at least 20seconds. In some embodiments, RF energy is delivered to target tissue ata level that decreases (e.g. one or more energy delivery parameterlevels decrease) over time. In some embodiments, RF energy deliverycomprises a modulated energy delivery, such as a pulse width modulatedenergy delivery with an “on” portion of the duty cycle below 20%. Insome embodiments, EDU 330 comprises an RF source comprising a 300 Wattsor less RF source, such as a 150 Watts or less RF source. In someembodiments, EDU 330 is configured to deliver an instantaneous power ofless than 300 Watts, or less than 260 Watts, such as an instantaneouspower than decreases to zero Watts over approximately 30 seconds. Insome embodiments, EDU 330 is configured to deliver RF energy in acurrent-driven mode. In some embodiments, EDU 330 is configured todeliver RF energy for at least 2 seconds, such as in a continuous and/orpulsed manner. In some embodiments, the frequency of RF energy ismaintained below 1.0 Mhz.

EDU 330, electrodes 136 a and 137 a and/or other components of system 10can be constructed and arranged to deliver RF energy to target tissuesuch that the temperature of at least a portion of the target tissuerises rapidly, such as at a rate of greater than or equal to 17.5° C.per second. The RF energy can be delivered to cause the temperature ofat least a portion of the target tissue to reach a setpoint temperaturebetween 60° C. and 90° C., such as a setpoint temperature between 65° C.and 80° C. System 10 can be constructed and arranged to cause the targettissue to elevate to a setpoint temperature and maintain that setpointtemperature, such as by maintaining the setpoint temperature for a timeperiod between 2 and 40 seconds. In these embodiments, the setpointtemperature can be between 60° C. and 90° C., such as a setpointtemperature between 75° C. and 85° C. that is maintained for between 15and 25 seconds. In some embodiments, after a setpoint temperature isachieved and/or maintained, the RF energy delivered causes a decrease intemperature over time, such as to match a tissue response of the targettissue.

Controller 360 can include a graphical user interface configured toallow one or more operators of system 10 to perform one or morefunctions such as entering of one or more system input parameters andvisualizing and/or recording of one or more system output parameters.Controller 360 can include one or more user input components (e.g. touchscreens, keyboards, joysticks, electronic mice and the like), and one ormore user output components (e.g. video displays; liquid crystaldisplays; alphanumeric displays; audio devices such as speakers; lightssuch as light emitting diodes; tactile alerts such as assembliesincluding a vibrating mechanism; and the like). Examples of system inputparameters include but are not limited to: type of energy to bedelivered such as RF energy, thermal energy and/or mechanical energy;quantity of energy to be delivered such as a cumulative number of joulesof energy to be delivered and/or peak amount of energy to be delivered;types and levels of combinations of energies to be delivered; energydelivery duration; pulse width modulation percentage of energydelivered; temperature of a fluid to be delivered to a expandableelement such as a balloon; temperature of a cooling fluid to bedelivered; flow rate of a hot fluid to be delivered; volume of a hotfluid to be delivered; number of reciprocating motions for an energydelivery element to transverse; temperature for a treatment assemblysuch as target temperature and/or maximum temperature; insufflationpressure; insufflation duration; and combinations of these. System inputparameters can include information based on patient anatomy and/orconditions such as pre-procedural and/or pen-procedural parametersselected from the group consisting of: mucosal density and/or thickness;mucosal “lift” off of submucosa after a submucosal injection;longitudinal location of target tissue within the GI tract; andcombinations of these. Examples of system output parameters include butare not limited to: temperature information such as tissue and/ortreatment assembly temperature information; pressure information such asballoon pressure information and/or insufflation pressure information;force information such as level of force applied to tissue information;patient information such as patient physiologic information recorded byone or more sensors; and combinations of these.

Controller 360 and/or one or more other components of system 10 caninclude an electronics module, such as an electronics module including aprocessor, memory, software, and the like. Controller 360 can beconfigured to allow an operator to initiate, modify and cease treatmentof target tissue by the various components of system 10, such as bycontrolling energy delivery unit 330 and/or fluid delivery unit 340.Controller 360 can be configured to modify one or more RF energydelivery parameters, such as a parameter selected from the groupconsisting of: voltage; current; frequency; pulse width modulationon-time and/or off-time; a time division multiplexing parameter; andcombinations of these. Controller 360 can be configured for manualcontrol, so that the operator first initiates the energy delivery, thenallows the associated ablation element to ablate the tissue for sometime period, after which the operator terminates the energy delivery.

Controller 360 and EDU 330 can be configured to deliver energy inconstant, varied, continuous and discontinuous energy delivery profiles.Pulse width modulation and/or time division multiplexing (TDM) can beincorporated to achieve precision of energy delivery, such as to ensureablation of target tissue while leaving non-target tissue intact.

In some embodiments, where system 10 is constructed and arranged toperform hot fluid ablation, controller 360 can be configured to adjustthe temperature, flow rate and/or pressure of fluid delivered toexpandable assembly 130 a and/or 130 b. Controller 360 can be configuredto initiate insufflation and/or to adjust insufflation pressure.Controller 360 can be configured to deliver energy (e.g. from fluiddelivery unit 340 and/or EDU 330) and/or other tissue treatment in aclosed-loop fashion, such as by modifying one or more tissue treatmentparameters based on signals from one or more sensors of system 10 suchas those described hereabove. Controller 360 can be programmable such asto allow an operator to store predetermined system settings for futureuse.

Controller 360 can comprise an impedance monitoring assembly, such as animpedance monitoring assembly that receives impedance information fromone or both of functional element 131 a of expandable assembly 130 aand/or functional element 131 b of expandable assembly 130 b. EDU 330can deliver RF energy to electrodes 136 a and/or 137 a based on theimpedance determined by the impedance monitoring assembly.

Numerous embodiments of the systems, methods and devices for treatingtarget tissue described hereabove include controlling and/or monitoringthe change in target tissue temperature to cause its ablation, such as atemperature increase above 43° C., typically above 60° C., 70° C. or 80°C., to ablate at least a portion of the target tissue TT. One or morecooling fluids can be delivered to limit or otherwise control ablation,such as to prevent damage to non-target tissue, such as the adventitiallayer of the duodenum or other small intestine segment. Fluid deliveryunit 340 can be constructed and arranged to deliver a fluid to tissueand/or a component and/or assembly of system 10, such as to warm and/orcool the tissue, component and/or assembly. Fluid delivery unit 340 canbe configured to deliver a cooling fluid to a luminal wall such as awall of the small intestine (e.g. a duodenal wall), such as prior to adelivery of RF energy, during a delivery of RF energy and/or after adelivery of RF energy. In some embodiments, a chilled fluid, such as afluid below 20° C., or below 10° C. is used to cool tissue prior to,during and/or after delivery of RF energy to tissue. In someembodiments, the chilled fluid is delivered between ablation of a firstportion of target tissue and a second portion of target tissue, such asto remove residual heat remaining after the first treatment. The coolingfluid can be delivered through functional element 131 a of expandableassembly 130 a and/or functional element 131 b of expandable assembly130 b, such as when functional element 131 a and/or 131 b comprises afluid delivery element such as a nozzle, an exit hole or a permeablemembrane. The cooling fluid can be supplied to expandable assembly 130 aand/or 130 b, such as when expandable assembly 130 a and/or 130 bcomprises a balloon configured to contact tissue. Alternatively oradditionally, fluid delivery unit 340 can be fluidly attached to anothercomponent of ablation device 100 and/or system 10, the attachedcomponent not shown but configured to deliver fluid to tissue and/or acomponent of system 10 such as to add and/or absorb heat. Fluid deliveryunit 340 can comprise a cryogenic source used to deliver fluids at lowtemperatures, such as temperatures below 0° C. Examples of fluidsdelivered include but are not limited to: liquids such as water and/orsaline; gases such as carbon dioxide, nitrogen, nitrous oxide and/orair; and combinations of these. Fluid delivery unit 340 can include adesiccant and/or drying assembly configured to dehydrate or otherwiseremove moisture from one or more delivered gases prior to theirdelivery.

System 10 can include a motion control mechanism, such as motiontransfer assembly 335. Motion transfer assembly 335 can be constructedand arranged to rotate, translate and/or otherwise move a component ofsystem 10, such as to move one or more of expandable assemblies 130 aand/or 130 b of ablation device 100. In some embodiments, motiontransfer assembly 335 is configured to rotate and/or axially translateshafts 111 a and/or 111 b such that expandable assemblies 130 a and/or130 b, respectively, are rotated and/or translated. Motion transferassembly 335 can be configured to rotate expandable assemblies 130 a and130 b independently or in unison. Motion transfer assembly 335 can beconfigured to translate expandable assembly 130 a as RF energy is beingdelivered by at least one of electrodes 136 a or 137 a. Motion transferassembly 335 can be configured to translate expandable assembly 130 abetween a first RF energy delivery and a second RF energy delivery.Motion transfer assembly 335 can include one or more rotational and/orlinear drive assemblies, such as those including rotational motors,magnetic and other linear actuators, and the like which are operablyconnected to shaft 111 a and/or 111 b. Shafts 111 a and/or 111 b areconstructed with sufficient column strength and/or torque transferproperties to sufficiently rotate and/or translate expandable assemblies130 a and/or 130 b, respectively. Motion transfer assembly 335 can be incommunication with controller 360, such as to activate, adjust and/orotherwise control motion transfer assembly 335 and thus the motion ofexpandable assemblies 130 a and/or 130 b. Motion transfer assembly 335can be manually driven and/or automatically (e.g. motor) driven.Alternatively or additionally, motion transfer assembly 335 can be usedto advance and/or retract expandable assemblies 130 a and/or 130 b froma first position to treat a first portion of target tissue, to a secondposition to treat a second portion of target tissue. In this embodiment,repositioning of expandable assemblies 130 a and/or 130 b can beconfigured to provide overlapping treatment, such as the overlappingtreatment described in reference to FIG. 3 herebelow.

System 10 can include a second ablation device 100′ constructed andarranged to treat target tissue TT. Second ablation device 100′ can beof similar or dissimilar construction to ablation device 100. In someembodiments, second ablation device 100′ comprises an expandableassembly with a different diameter than expandable assembly 130 a ofdevice 100. In some embodiments, second ablation device 100′ comprisesan electrode with a different pattern of conductors than electrode 136 aand/or 137 a of device 100. In some embodiments, second ablation device100′ comprises a device selected from the group consisting of: hot fluidfilled balloon device; vapor ablation device; cryoablation device; laserablation device; ultrasound ablation device; and combinations of these.

System 10 can further include one or more imaging devices, such asimaging device 370. Imaging device 370 can be configured to be insertedinto the patient and can comprise a visual light camera; an ultrasoundimager; an optical coherence domain reflectometry (OCDR) imager; and/oran optical coherence tomography (OCT) imager, such as when integral to,attached to, contained within and/or proximate to shaft 111 a and/or 111b. Imaging device 370 can be inserted through a separate working channelof endoscope 350, lumen not shown. In one embodiment, imaging device 370is an ultrasound transducer connected to a shaft, not shown butsurrounded by shaft 111 a and typically rotated and/or translated tocreate a multi-dimensional image of the area surrounding imaging device370. Alternatively or additionally, imaging device 370 can be externalto the patient, such as an imaging device selected from the groupconsisting of: an X-ray; a fluoroscope; an ultrasound image; an MRI; aPET Scanner; and combinations of these. Image and other informationprovided by imaging device 370 can be provided to an operator of system10 and/or used by a component of system 10, such as controller 360, toautomatically or semi-automatically adjust one or more system parameterssuch as one or more energy delivery parameters.

System 10 can further include protective element 380, constructed andarranged to be positioned on, over and/or otherwise proximate non-targettissue to prevent damage to the non-target tissue during energy deliveryand/or other tissue treatment event. Protective element 380 can comprisean element selected from the group consisting of: a deployable and/orrecoverable cap and/or covering; an advanceable and/or retractableprotective sheath; and combinations of these. Protective element 380 canbe delivered with endoscope 350 and/or another elongate device such thatelement 380 can be placed over or otherwise positioned to protectnon-target tissue, such as tissue selected from the group consisting of:Ampulla of Vater, bile duct, pancreas, pylorus, muscularis externae,serosa; and combinations of these. In a typical embodiment, protectiveelement 380 is removed within 24 hours of placement, such as by beingremoved during the procedure after treatment of the target tissue TT.

System 10 can be constructed and arranged to prevent excessivedistension of a segment of the small intestine (e.g. a segment of theduodenum), such as to prevent application of a force that could causetearing of the serosa. In some embodiments, system 10 is constructed andarranged such that all tissue contacting components and/or fluidsdelivered by system 10 maintain forces applied on a gastrointestinalwall below 2.5 psi, such as less than 1 psi. System 10 can beconstructed and arranged such that one or more radial expandableassemblies 130 or other radial expandable assemblies or elements apply aforce of at least 0.2 psi, such as a force of at least 0.5 psi, such asto improve the quality of apposition of the radially expandable elementor assembly. System 10 can be constructed and arranged to avoid orotherwise minimize damage to the muscularis layer of thegastrointestinal tract, such as by controlling energy delivery and/or byminimizing trauma imparted by one or more components of system 10.

System 10 can further include one or more pharmaceutical and/or otheragents 500, such as an agent configured for systemic and/or localdelivery to a patient. Agents 500 can be delivered pre-procedurally,pen-procedurally and/or post-procedurally. Agents 500 can be configuredto improve healing, such as agents selected from the group consistingof: antibiotics; steroids; mucosal cytoprotective agents such assucralfate; proton pump inhibitors and/or other acid blocking drugs; andcombinations of these. Alternative or in addition to agents 500,pre-procedural and/or post-procedural diets can be employed.Pre-procedural diets can include food intake that is low incarbohydrates and/or low in calories. Post-procedural diets can includefood intake that comprise a total liquid diet and/or a diet that is lowin calories and/or low in carbohydrates.

In some embodiments, system 10 does not include a chronically implantedcomponent and/or device, such as where system 10 includes only bodyinserted devices that are removed at the end of the clinical procedureor shortly thereafter, such as devices removed within 8 hours ofinsertion, within 24 hours of insertion and/or within one week ofinsertion. In an alternative embodiment, implant 510 can be included.Implant 510 can comprise at least one of: a stent; a sleeve; and/or adrug delivery device such as a coated stent, a coated sleeve and/or animplanted pump. Implant 510 can be inserted into the patient and remainimplanted for a period of at least one month, at least 6 months or atleast 1 year.

Each of the components of system 10 can be removably attached to anothercomponent, particularly ablation device 100, controller 360, energydelivery unit 330, motion transfer element 335, fluid delivery unit 340,ground pad 332, endoscope 350 and/or second ablation device 100′.Typical attachment means include but are not limited to mechanical orelectromechanical connectors providing an electrical, optical and/orfluidic connection.

Referring now to FIG. 2, a side sectional view of the distal portion ofan ablation device inserted into a duodenum is illustrated, consistentwith the present inventive concepts. Ablation device 100 comprises shaft110, a relatively flexible, biocompatible, elongate structure configuredfor insertion into a body lumen, such as a lumen of the small intestine,such as the duodenal lumen shown. Shaft 110 is typically connected to ahandle on its proximal end, not shown but configured to allow anoperator to advance, retract and otherwise manipulate or controlablation device 100. Ablation device 100 can be constructed and arrangedfor delivery over a guidewire, via a lumen from a proximal portion to adistal portion, or via a rapid exchange sidecar in the distal portion ofthe device (lumen and sidecar not shown but well known to those of skillin the art). Expandable assembly 130 is mounted to a distal portion ofshaft 110, and can comprise an inflatable balloon, cage or otherexpandable element as described in reference to FIG. 1 hereabove. Shaft110 is shown inserted through introducer 115 which can comprise anendoscope, sheath, or other body introduction device. Expandableassembly 130 has been positioned in a portion of duodenal tissue thathas had a segment of submucosal tissue expanded (e.g. a fullcircumferential segment of at least 50% of the duodenal submucosaexpanded), such as has been described above. Expandable assembly 130comprises two ablation elements, electrodes 136 and 137, each comprisesmultiple interdigitated elongate conductors as shown in FIG. 2 anddescribed in detail in reference to FIG. 2A herebelow. Expandableassembly 130 has been radially expanded such as to contact the mucosalsurface of the duodenum. Electrodes 136 and 137 are connected to wires138 and 139, respectively, and constructed and arranged to be attachedto an RF energy delivery source, such as EDU 330 of FIG. 1. Electrodes136 and 137 can cover the full circumference (e.g. approximately 360°)of expandable assembly 130 or they can cover a partial circumference(e.g. an area covering between 45° and 300° of the outer surface ofexpandable assembly 130).

Referring additionally to FIG. 2A, a magnified view of electrodes 136and 137 of FIG. 2 is illustrated, consistent with the present inventiveconcepts. Electrode 136 comprises multiple elongate conductors 132, eachelectrically connected to wire 138, and electrode 137 comprises multipleelongate conductors 133 each electrically connected to wire 139.Conductors 132 and 133 are typically in the interdigitated pattern shownsuch that RF energy can be delivered between the alternative pairs ofrelatively parallel conductors 132 of electrode 136 and conductors 133of electrode 137. When expandable assembly 130 is expanded to contacttissue such as mucosal tissue, and RF energy is applied betweenelectrodes 136 and 137, current passes from neighboring edges ofconductors 132 and 133, through the contacted tissue, causing heating ofthe tissue. This heating, combined with conductive heating that occursin neighboring tissue, ablates the tissue as has been described inreference to FIG. 1 hereabove. The spacing between the edges of theassociated pairs of conductors 132 and 133 is termed herein“edge-to-edge” spacing and illustrated in FIG. 2A. Delivery of RF energybetween the various pairs of conductors 132 and 133 is configured tocause at least ablation of the mucosa of the small intestine (e.g.duodenal mucosa). Ablation of at least a portion of the depth of thesmall intestine submucosa is typically caused by the RF energy deliveredand resultant conductive heating. However, ablation of deeper layers,such as the adventitial layers (e.g. muscularis layers and/or serosallayers) is prevented or otherwise reduced to a near atraumatic level.After adequate energy delivery, expandable assembly 130 will berepositioned in a more distal segment of duodenum, with or withoutradially compacting assembly 130. Subsequently, a second energy deliverycan be performed. The steps of repositioning and delivering energy arerepeated until an adequate portion of small intestine is treated,typically greater than 50% of the length of the duodenal mucosa, orgreater than 90% of the duodenal mucosa length. Alternatively oradditionally, other tissue can be treated, such as has been describedhereabove.

Conductors 132 and/or 133 comprise elongate structures whose major axisis positioned relatively parallel to the central axis of a body lumenwhen expandable assembly 130 is expanded within the body lumen.Conductors 132 and/or 133 and expandable assembly 130 can be constructedand arranged such that conductors 132 and/or 133 remain relativelyparallel to the central axis of a body lumen when neighboring and/orwithin a curvilinear portion of that body lumen. Conductors 132 and/or133 can be at least 10 mm long, such as at least 20 mm long. Conductors132 and 133 can be arranged in the interdigitated pattern shown in FIG.2A, such that bipolar RF energy passes between neighboring pairs ofconductors. Conductors 132 and 133 can have an edge-to-edge spacing asdescribed in reference to FIG. 1 hereabove. One or more pairs ofconductors 132 and 133 can be arranged to remain relatively parallelwhen expandable assembly 130 is radially expanded. Electrodes 136 and/or137 can include at least four conductors 132 and/or 133, respectively.

Referring now to FIG. 3, a side sectional view of the distal portion ofan ablation device inserted into a curvilinear section of duodenum isillustrated, consistent with the present inventive concepts. Ablationdevice 100 comprises shaft 110, a relatively flexible, biocompatible,elongate structure configured for insertion into a body lumen, such as alumen of the small intestine, such as the duodenal lumen shown. Shaft110 is typically connected to a handle on its proximal end, not shownbut configured to allow an operator to advance, retract and otherwisemanipulate or control ablation device 100. Ablation device 100 can beconstructed and arranged for delivery over a guidewire, via a lumen froma proximal portion to a distal portion, or via a rapid exchange sidecarin the distal portion of the device (lumen and sidecar not shown butwell known to those of skill in the art). Expandable assembly 130 ismounted to a distal portion of shaft 110, and can comprise an inflatableballoon, cage or other expandable element as described in reference toFIG. 1 hereabove. Shaft 110 is shown inserted through introducer 115which can comprise an endoscope, sheath, or other body introductiondevice. Expandable assembly 130 comprises an array of ablation elements,conductor array 135, such as an array of two or more electrodes whichcover a full or partial circumferential portion of expandable assembly130. In some embodiments, array 135 comprises multiple interdigitatedelongate conductors between which bipolar RF energy is delivered, as hasbeen described hereabove. Expandable assembly 130 has been positioned ina distal portion of duodenal tissue, such as a section that has had asegment of submucosal tissue expanded (expansion not shown but describedin detail in reference to FIG. 2 hereabove). Relative tissue layerthicknesses and other relative dimensions shown in FIG. 3 are not toscale. Expandable assembly 130 has been radially expanded such as tocontact the mucosal surface of the duodenum at a 1^(st) target tissueportion, which is distal to a series of target tissue portionscomprising sequential target tissue portions 2 through 6 as shown inFIG. 3. Conductor array 135 is electrically connected to at least twowires, wires 138 and 139, which are constructed and arranged to beattached to an RF energy delivery source, such as EDU 330 of FIG. 1.

Expandable assembly 130 is sized to allow positioning in the curvedsegments of the gastrointestinal tract, such as a curved segment of theduodenum, such that expandable assembly 130 can be expanded to fullycontact the mucosal wall without exerting undesired force onto tissue.In some embodiments, the length expandable assembly 130 is less than orequal to 30 mm, such as less than or equal to 25 mm, less than or equalto 20 mm or less than or equal to 15 mm. After application of RF energy(e.g. monopolar RF energy, bipolar RF energy and/or combined monopolarand bipolar RF energies), expandable assembly 130 will be repositionedto the 2^(nd) target tissue portion, just proximal to the 1^(st) targettissue portion, with or without contracting assembly 130 prior to therepositioning. Subsequently, second energy delivery can be performed.The steps of repositioning and delivering energy are repeated untiltarget tissue portions 3, 4, 5 and 6 have been treated, typicallygreater than 50% of the length of the duodenal mucosa, or greater than90% of the duodenal mucosal length. Alternatively or additionally, othertissue can be treated, such as has been described hereabove.

Target tissue portions 1 through 6 typically include common oroverlapping tissue portions, such as is shown in FIG. 3. While theembodiment of FIG. 3 shows six target tissue portions being treated,more or less segments can be treated. Treatments (e.g. energydeliveries) are typically done in a contiguous manner (e.g. 1^(st)portion followed by 2nd portion, followed by 3rd portion, etc), howeverany order can be performed.

Referring now to FIG. 4A, perspective and magnified end views of thedistal portion of an ablation device comprising a foldable assembly isillustrated, consistent with the present inventive concepts. Ablationdevice 100 comprises shaft 110, a relatively flexible, biocompatible,elongate structure configured for insertion into a body lumen, such as alumen of the small intestine, such as a duodenal lumen. Shaft 110 istypically connected to a handle on its proximal end, not shown butconfigured to allow an operator to advance, retract and otherwisemanipulate or control ablation device 100. Ablation device 100 can beconstructed and arranged for delivery over a guidewire, via a lumen froma proximal portion to a distal portion, or via a rapid exchange sidecarin the distal portion of the device (lumen and sidecar not shown butwell known to those of skill in the art). Expandable assembly 130 ismounted to a distal portion of shaft 110. Shaft 110 is shown insertedthrough introducer 115 which can comprise an endoscope, sheath, or otherbody introduction device. Expandable assembly 130 includes substrate134, a sheet of material which is constructed and arranged to be foldedand/or unfolded to radially compacted and expanded conditions,respectively. Substrate 134 can be flexible, and can include one or moreheat set folds. Substrate 134 is shown in its radially compacted statein FIG. 4A. In FIG. 4B, a perspective view of the device of FIG. 4A isshown, with expandable assembly 130 in a partially expanded (e.g.partially unfolded). In FIG. 4C, a perspective view of the device ofFIG. 4A is shown, with expandable assembly 130 in a fully expandedstate. Substrate 134 comprises an array of conductors 135, which havebeen removed from FIGS. 4A and 4B for illustrative clarity. Substrate134 can be configured to be folded and/or unfolded via one or morecontrol mechanisms, not shown but such as the control rod described inreference to FIG. 10 herebelow. A control rod or other mechanism can beconfigured to be rotated and/or translated to fold and/or unfoldsubstrate 134. Numerous mechanisms and/or configurations can be used tofold or unfold expandable assembly 130, such as a balloon attached tosubstrate 134 and positioned to unfold when the balloon is inflated orfold when the balloon is deflated (e.g. a negative pressure is appliedto the balloon via one or more inflation tubes or lumens). In someembodiments, introducer 115 can be used to capture (e.g. cause to fold)substrate 134. In some embodiments, substrate 134 can be biased in afolded, partially folded, or fully unfolded states, such as via one ormore heat sets used to create folds in a flexible material such asmaterial selected from the group consisting of: polyamide; a polyesterweave; a stretchable polyurethane material; and combinations of these.

Referring now specifically to FIG. 4C, expandable assembly 130 has beenradially expanded such as to contact the mucosal surface of the smallintestine (tissue not shown). Conductor array 135, now shown, cancomprise one or more electrodes, such as one or more electrodescomprising an array of conductors, such as an array of two or moreelectrodes which cover a full or partial circumferential portion ofexpandable assembly 130. In some embodiments, array 135 comprisesmultiple interdigitated elongate conductors between which bipolar RFenergy is delivered, as has been described hereabove in reference toFIG. 2A. Conductor array 135 is electrically connected to at least twowires, wires 138 and 139, which can be constructed and arranged to beattached to an RF energy delivery source, such as EDU 330 of FIG. 1.

Expandable assembly 130 can be sized to allow positioning in the curvedsegments of a gastrointestinal segment, such that expandable assembly130 can be expanded to fully contact the mucosal wall without exertingundesired force onto tissue. In some embodiments, the length expandableassembly 130 is less than or equal to 30 mm, such as less than or equalto 25 mm, less than or equal to 20 mm or less than or equal to 15 mm.After application of RF energy (e.g. monopolar RF energy, bipolar RFenergy and/or combined monopolar and bipolar RF energies), expandableassembly 130 can be repositioned for subsequent treatment of one or moreadditional target tissue portions, as has been described in reference toFIGS. 2 and 3 hereabove.

Referring now to FIGS. 5A and 5B, side views of the distal portion of anablation device comprising a helical coil are illustrated, consistentwith the present inventive concepts. Ablation device 100 comprises shaft110, a relatively flexible, biocompatible, elongate structure configuredfor insertion into a body lumen such as a lumen of the small intestine.Shaft 110 is typically connected to a handle on its proximal end, notshown but configured to allow an operator to advance, retract andotherwise manipulate or control ablation device 100. Ablation device 100can be constructed and arranged for delivery over a guidewire, via alumen from a proximal portion to a distal portion, or via a rapidexchange sidecar in the distal portion of the device (lumen and sidecarnot shown but well known to those of skill in the art). Continuous withshaft 110 is expandable assembly 130, a flexible tube mounted to thedistal end of shaft 110, typically with a diameter approximating thediameter of the distal portion of shaft 110. Shaft 110 is shown insertedthrough introducer 115 which can comprise an endoscope, sheath, or otherbody introduction device. Expandable assembly 130 surrounds acurvilinear mandrel 113, typically a stainless steel, nickel titaniumalloy or plastic filament which is biased in the helical configurationshown, and travels proximally within shaft 110 to its proximal end.Curvilinear mandrel 113 and expandable assembly 130 are constructed andarranged so that they can be radially compressed, such as to be capturedwithin introducer 115.

Mounted to the distal end or a distal portion of shaft 110 areelectrodes 136 and 137, such as two or more ring shaped electrodessurrounding a segment of expandable assembly 130. Electrodes 136 and 137are each electrically attached to one or more wires, as has beendescribed hereabove, traveling on, in or within shaft 110 to beattachable to an energy delivery unit, such as EDU 330 of FIG. 1. Insome embodiments, three or more electrodes are included on expandableassembly 130. Expandable assembly 130 and curvilinear mandrel 113 areconstructed and arranged such that the deployed helix circumferentiallycontacts gastrointestinal wall tissue, such as mucosal tissue of theduodenum or other small intestine location. Subsequently, electrodes 136and 137 contact the tissue, such that RF energy can be delivered by orbetween electrodes 136 and 137 as has been described hereabove. In someembodiments, electrodes 136 and/or 137 can be covered by a dielectricmaterial, and RF energy delivered to tissue through capacitive coupling,such as is described in reference to FIG. 10A herebelow.

In some embodiments, after sufficient energy has been delivered to aportion of target tissue, shaft 110 is retracted (e.g. via one or morecontrols on a proximal handle not shown), causing expandable assembly130 to equally retract and electrodes 136 and 137 to be positionedproximate a different portion of target tissue. A subsequent energydelivery can be performed, and the repositioning and energy deliverysteps repeated until a sufficient portion of gastrointestinal tissue istreated. In some embodiments, energy can be delivered as shaft 110 isretracted (e.g. as electrodes 136 and 137 move along a tissue surface),such as via a manual (e.g. operator driven) and/or automatic (e.g. via amotion transfer assembly such as motion transfer assembly 335 of FIG. 1)retraction. While the foregoing has been described in terms ofretraction, advancement of shaft 110 can be performed to repositionelectrodes 136 and 137, between and/or during energy deliveries.

Expandable assembly 130 and curvilinear mandrel 113 can be constructedand arranged to allow sufficient contact in curved segments of agastrointestinal segment, such that expandable assembly 130 can beexpanded to fully contact the mucosal wall without exerting undesiredforce onto tissue.

Referring now to FIG. 6, a side view of the distal portion of anablation device including multiple expandable assemblies is illustrated,consistent with the present inventive concepts. Ablation device 100comprises shaft 110, a relatively flexible, biocompatible, elongatestructure configured for insertion into a body lumen such as the lumenof the small intestine. Shaft 110 is typically connected to a handle onits proximal end, not shown but configured to allow an operator toadvance, retract and otherwise manipulate or control ablation device100. Ablation device 100 can be constructed and arranged for deliveryover a guidewire, via a lumen from a proximal portion to a distalportion, or via a rapid exchange sidecar in the distal portion of thedevice (lumen and sidecar not shown but well known to those of skill inthe art). Ablation device 100 comprises a first expandable assembly 130a, a more distal second expandable assembly 130 b, and a further distalthird expandable assembly 130 c, each shown in their radially expandedcondition. Expandable assemblies 130 a, 130 b and/or 130 c each cancomprise an inflatable balloon, cage or other expandable element asdescribed in reference to FIG. 1 hereabove. Shaft 110 is shown insertedthrough introducer 115 which can comprise an endoscope, sheath, or otherbody introduction device. Expandable assemblies 130 a, 130 b and 130 ceach comprise an array of conductors, arrays 135 a, 135 b and 135 c,respectively, each connected to one or more wires as shown, andconstructed and arranged to receive electrical energy as has beendescribed in detail hereabove. In some embodiments, ablation device 100includes four or more expandable assemblies, such as four or moreexpandable assemblies each comprise an array of conductors.

Expandable assemblies 130 a, 130 b and/or 130 c are sized to allowpositioning in the curved segments of a gastrointestinal segment such asa curved segment of the small intestine (e.g. a curved segment of theduodenum), such that each expandable assembly 130 a, 130 b and 130 c canbe expanded to fully contact the mucosal wall without exerting undesiredforce onto tissue. In some embodiments, the length of expandableassemblies 130 a, 130 b and/or 130 c is less than or equal to 30 mm,such as less than or equal to 25 mm, less than or equal to 20 mm, orless than or equal to 15 mm. In some embodiments, two or more ofexpandable assemblies 130 a, 130 b and/or 130 c comprises a length ofless than or equal to 20 mm. In some embodiments, expandable assemblies130 a, 130 b and/or 130 c comprise similar lengths and/or expandeddiameters. In some embodiments, expandable assemblies 130 a, 130 band/or 130 c comprise different lengths and/or expanded diameters.Expandable assemblies 130 a, 130 b and/or 130 c can be separated bysimilar or different separation distances. In some embodiments,expandable assemblies 130 a, 130 b and/or 130 c are separated by adistance less than the length of the next assembly distal to it, suchthat untreated target tissue can be treated by retracting shaft 110 andperforming a second ablation.

In some embodiments, conductor arrays 135 a, 135 b and 135 c comprisesimilar configurations of conductors. In other embodiments, such as theembodiment of FIG. 6, conductor arrays 135 a, 135 b and 135 c comprisedifferent configurations of conductors. For example, conductor arrays135 a and 135 b contain pairs of relatively linear conductors that areradially offset from each other. In this offset configuration, energycan be applied to conductor array 135 b to treat a partialcircumferential segment of gastrointestinal tissue while expandableassembly 130 b is at a first axial location. Subsequently, shaft 110 canbe advanced such that expandable assembly 130 a moves distally to bepositioned in the same first axial location. Delivery of energy toconductor array 135 a will cause a different target tissue portion to betreated due to the offset in conductor patterns between array 135 b and135 a. Each of the conductor arrays 135 a, 135 b and 135 c, can compriselinear or curvilinear conductors, such as the curvilinear conductorpairs included in expandable assembly 130 c.

After application of RF energy (e.g. monopolar RF energy, bipolar RFenergy and/or combined monopolar and bipolar RF energies), shaft 110 canbe advanced or retracted to position each of expandable assemblies 130a, 130 b and 130 c in new locations. Energy delivery can be performedduring or after translation of shaft 110, and until a sufficient lengthof tissue has been treated, as has been described hereabove. In someembodiments, the target tissue comprises a set of sequential targettissue portions comprising, in order, a first section, a second section,a third section, a fourth section, and a fifth section, for examplewhere the expandable assemblies 130 a, 130 b and 130 c are positioned toablate the first, third and fifth target tissue portions in a firstenergy delivery and expandable assemblies 130 a and 130 b are positionedto ablate the second and fourth target tissue portions in a secondenergy delivery.

Referring now to FIG. 7, a side sectional view of a distal portion of anablation device including an expandable assembly comprising a balloonsurrounding an expandable scaffold is illustrated, consistent with thepresent inventive concepts. Ablation device 100 comprises shaft 110, arelatively flexible, biocompatible, elongate structure configured forinsertion into a body lumen such as a lumen of the small intestine (e.g.into the duodenal lumen). Shaft 110 is typically connected to a handleon its proximal end, not shown but configured to allow an operator toadvance, retract and otherwise manipulate or control ablation device100. Ablation device 100 can be constructed and arranged for deliveryover a guidewire, via a lumen from a proximal portion to a distalportion, or via a rapid exchange sidecar in the distal portion of thedevice (lumen and sidecar not shown but well known to those of skill inthe art). Ablation device 100, and the other ablation devices of thepresent inventive concepts, can include a flexible guidewire tip, suchas guidewire tip 116 shown in FIG. 7, configured to support atraumaticadvancement of device 100 through a gastrointestinal lumen. Shaft 110 isshown inserted through introducer 115 which can comprise an endoscope,sheath, or other body introduction device.

Expandable assembly 130 is mounted to a distal portion of shaft 110, andincludes an expandable inner cage comprising multiple splines 141 whichare attached at their distal ends to hub 144 and at their proximal endsto the distal end of inner shaft 111. Expandable assembly 130 furtherincludes balloon 142 surrounding splines 141. Balloon 142 includesmultiple openings 143 as shown. Openings 143 are positioned to coincidewith electrodes 136 and 137, each comprising the multiple elongateconductors shown, mounted to alternating splines 141. In someembodiments, electrodes 136 and/or electrodes 137 comprise a widthgreater than a diameter of openings 130. In some embodiments, electrodes136 and/or electrodes 137 comprise a length greater that a diameter ofopenings 130. Balloon 142 and openings 143 are constructed and arrangedsuch that tissue contacts electrodes 136 and 137 at the predetermined,fixed locations of openings 143, when expandable assembly 130 ispositioned in gastrointestinal tissue in its radially expanded state.Openings 143 can comprise one or more different shaped openings, such asopenings with a perimeter comprising a geometry selected from the groupconsisting of; a circle; an oval; and a rectangle.

Splines 141 can be resiliently biased in a radially expanded condition,such as stainless steel or nickel titanium alloy splines biased in thebowed condition shown. Alternatively, one or more control rods can beincluded to control expansion, not shown but described in detail inreference to FIG. 10 herebelow. Expandable assembly 130 and splines 141can be captured such as via retraction of shaft 110 to cause capturewithin introducer 115, and/or retraction of shaft 111 to cause capturewithin shaft 110. Electrodes 136 and 137 can comprise a circumferentialarray of conductors that cover the full circumference (e.g.approximately 360°) of expandable assembly 130 or the array can cover apartial circumference (e.g. an area covering between 45° and 300° of theouter surface of expandable assembly 130). In some embodiments, balloon142 does not include openings 143, and monopolar and/or bipolar RFenergy can be delivered to tissue via capacitive coupling throughballoon 142 functioning as a dielectric between electrodes 136 and/or137 and the target tissue. In some embodiments, one or more electrodescan be positioned on the outer surface of balloon 142, such as one ormore electrodes constructed and arranged to deliver monopolar and/orbipolar RF energy to target tissue.

Electrodes 136 and 137 are connected to one or more wires, not shown butconfigured to deliver monopolar and/or bipolar RF energy to electrodes136 and 137, and treat at least a portion of target tissue as describedhereabove. After adequate energy delivery, expandable assembly 130 canbe repositioned in a different segment of gastrointestinal tissue, withor without radially compacting assembly 130. Subsequently, a secondenergy delivery can be performed. The steps of repositioning anddelivering energy are repeated until the desired complete segment oftarget tissue is treated. In some embodiments, the target tissuecomprises greater than 50% of the length of the duodenal mucosa, orgreater than 90% of the duodenal mucosa length. Alternatively oradditionally, other tissue can be treated, such as has been describedhereabove.

Referring now to FIG. 8A, a side view of a conductor array including twoelectrodes each comprising multiple elongate conductors is illustrated,consistent with the present inventive concepts. Conductor array 135comprises substrate 134 onto which electrodes 136 and 137 are attached.Electrodes 136 and 137 comprise multiple elongate conductors in theinterdigitated, parallel pattern shown in FIG. 8A. Electrodes 136 and/or137 can be attached to substrate 134 in various ways, such as with anadhesive bond or mechanical connection such as a weld or swage. In someembodiments, electrodes 136 and/or 137 are deposited onto substrate 134,such as via an ink-jet deposition such as an ink-jet deposition in whichcatalytic ink is deposited and then exposed to a copper solution. Insome embodiments, electrodes 136 and/or 137 are deposited onto substrate134 using a masked deposition process.

Electrodes 136 and 137 are attached on their proximal ends to wires 138and 139, respectively, such as to be attached to wires of an ablationdevice as has been described hereabove. In some embodiments, substrate134 comprises material selected from the group consisting of: polyamide;a polyester weave; a stretchable polyurethane material; and combinationsof these. Substrate 134 can be biased in the flat configuration shown inFIG. 8A, or it can include a resilient bias, such as a bias into a tubeshape. Electrodes 136 and 137 comprise an array of conductors coveringsubstantially the entire surface area of substrate 134, such that whensubstrate 134 is transitioned to a tubular configuration, electrodes 136and 137 can deliver RF energy to substantially a full circumferentialportion of tubular tissue, such as a segment of small intestine mucosaltissue (e.g. duodenal mucosal tissue).

Substrate 134 can be to be positioned on the distal end or on a distalportion of a shaft, such as shaft 110 described in reference to numerousfigures hereabove, and configured to radially expand to contact luminalwall tissue and/or radially compact to be captured by the shaft of anablation device. Alternatively, substrate 134 can be mounted to anexpandable element, such as a balloon; an expandable cage; a stent-likestructure; an array of splines; and combinations of these. In theseembodiments, substrate 134 comprises a flexibility sufficient toaccommodate the expansion and/or contraction of the expandable elementto which it is mounted. In alternative embodiments, three or moreelectrodes are included on substrate 134.

Referring now to FIG. 8B, a side view of a conductor array including twoelectrodes each comprising multiple elongate conductors is illustrated,consistent with the present inventive concepts. Conductor array 135 isof similar construction and arrangement as conductor array 135 of FIG.8A, with the exception that the conductors of electrodes 136 and 137cover less than substantially the full surface area of substrate 134. Inthis configuration, a full circumferential ablation is typicallyperformed by a first energy delivery, a rotation of array 135, and atleast a subsequent second energy delivery. Electrodes 136 and 137 areattached on their proximal ends to wires 138 and 139, respectively, asshown. Wires 138 and 139 can be attached to one or more conductors of anablation catheter, such as to deliver energy to electrodes 136 and 137,respectively, as has been described hereabove.

Referring now to FIG. 8C, a side view of a conductor array including twoelectrodes each comprising multiple elongate conductors is illustrated,consistent with the present inventive concepts. Conductor array 135comprises substrate 134 onto which multiple electrodes are mounted.Substrate 134 can be of similar materials, construction and arrangement,and it can be attached to a shaft, deployed in a lumen, and/or deliverenergy as described in reference to substrate 134 of FIG. 8A.

Conductor array 135 of FIG. 8C comprises multiple, varying shapeelectrodes such as round shaped electrodes 136 a and 137 a, triangleshaped electrodes 136 b and 137 b, rectangle shaped electrodes 136 c and137 c, and trapezoid shaped electrodes 136 d and 137 d. Conductor array135 can comprise various shapes and orientations of electrodes, pairs ofelectrodes, conductors and/or pairs of conductors, such as those shownin FIG. 8C or otherwise. Conductors of conductor array 135 can comprisea shape selected from the group consisting of: rectangle; square;triangle; trapezoid; and combinations of these. Alternatively oradditionally, electrodes 136 a-d and/or 137 a-d can be constructed andarranged to treat a target tissue portion with a shape selected from thegroup consisting of: rectangle; square; triangle; trapezoid; andcombinations of these. Electrodes 136 a-d and electrodes 137 a-d areconnected to wire bundles 138′ and 139′, respectively. Wire bundles 138′and 139′ can comprise a single conductor, such that each group ofelectrodes are electrically connected, or it bundles 138′ and 139′ cancomprise multiple, independent conductors, such that that each electrodecan be electrically isolated.

Referring now to FIG. 8D, side and end views of an expandable assemblyincluding a helical array of conductors are illustrated, consistent withthe present inventive concepts. Expandable assembly 130 comprisessubstrate 134, configured in the tubular construction shown. Expandableassembly 130 can be attached to the distal end or distal portion of ashaft, such as has been described above. Expandable assembly cancomprise an expandable element configured to radially expand and/orcontract, not shown but typically a balloon, expandable cage or otherexpandable element as has been described hereabove.

Expandable assembly 130 includes electrodes 136 and 137, each comprisingthe alternating helical geometry shown in FIG. 8D, each helix fixedlymounted to substrate 134 as has been described hereabove. Electrodes 136and 137 are electrically attached to wires 138 and 139, respectively,such that monopolar and/or bipolar RF energy can be applied to orbetween electrodes 136 and 137 as has been described hereabove.

Substrate 134 of FIGS. 8A-C can be attached to one or more expandableassemblies, such as an array of three or more expandable splines, suchthat substrate 134 and electrodes 136 and 137 mounted thereon, can beexpanded such as to contact target tissue. Referring now to FIG. 8E,expandable assembly 130′ comprises substrate 134 attached to threesplines 141. Splines 141 are constructed and arranged to expand asshown, such that substrate 134 and mounted electrodes 136 and 137comprise a relatively triangular cross sectional geometry. Targettissue, such as tubular target tissue such as a segment of smallintestine tissue, can be distended or otherwise manipulated toelectrically contact electrodes 136 and 137 while substrate 134 isexpanded to this relatively triangular cross sectional geometry.Referring now to FIG. 8F, expandable assembly 130″ comprises substrate134 attached to four splines 141. Splines 141 are constructed andarranged to expand as shown, such that substrate 134 and mountedelectrodes 136 and 137 comprise a relatively square cross sectionalgeometry. Target tissue, such as tubular target tissue such as a segmentof small intestine tissue, can be distended or otherwise manipulated toelectrically contact electrodes 136 and 137 while substrate 134 isexpanded to this relatively square cross sectional geometry. Referringnow to FIG. 8G, expandable assembly 130′″ comprises substrate 134attached to five splines 141. Splines 141 are constructed and arrangedto expand as shown, such that substrate 134 and mounted electrodes 136and 137 comprise a relatively pentagonal cross sectional geometry.Target tissue, such as tubular target tissue such as a segment of smallintestine tissue, can be distended or otherwise manipulated toelectrically contact electrodes 136 and 137 while substrate 134 isexpanded to this relatively pentagonal cross sectional geometry. Itshould be appreciated that six or more splines 141 can be included, suchas to expand substrate 134 to a hexagonal or other non-circulargeometry. Electrodes 136 and 137 of FIGS. 8E-8G can be connected to oneor more electrical wires, not shown but traveling proximally forattachment to a source of electrical energy as has been describedhereabove.

Referring now to FIGS. 9A, 9B and 9C, distal portions of three ablationdevices with three different tissue contacting portions are illustrated,consistent with the present inventive concepts. Ablation devices 100 a,100 b and 100 c of FIGS. 9A, 9B and 9C, respectively, are each shownexiting an introducer 115, as has been described hereabove. Ablationdevices 100 a-c each include shaft 110. Each shaft 110 can include asteering assembly comprising a pull wire 146 attached at its distal endto anchor 147, and at its proximal end to a control on a handle, controland handle not shown but configured to steer the distal portion of shaft110 by translating pull wire 146. Ablation device 100 a of FIG. 9Aincludes a round array of conductors 135 a. Ablation device 100 b ofFIG. 9B includes a triangle shaped array of conductors 135 b. Ablationdevice 100 c of FIG. 9C includes a rectangle shaped array of conductors135 c. In other embodiments, various other shapes can be employed for anarray of conductors, such as one or more shapes used to treat asimilarly shaped target tissue portion, or a target tissue portion thatcan be treated by sequentially delivering electrical energy to tissuethrough arrays of these one or more shapes. Typical shapes include butare not limited to: triangle; rectangle; pentagon; hexagon; trapezoid;and combinations of these. Conductor arrays 135 a-c are connected to oneor more wires, not shown but traveling proximally through shaft 110 suchas to be attached to an energy delivery unit (e.g. EDU 330 of FIG. 1)such that bipolar and/or monopolar RF energy can be delivered to targettissue.

Referring now to FIG. 10, the distal portion of an ablation devicecomprising multiple spline-mounted electrodes is illustrated, consistentwith the present inventive concepts. Ablation device 100 comprises shaft110, a relatively flexible, biocompatible, elongate structure configuredfor insertion into a body lumen such as a lumen of the small intestine.Shaft 110 is typically connected to a handle on its proximal end, notshown but configured to allow an operator to advance, retract andotherwise manipulate or control ablation device 100. Ablation device 100can be constructed and arranged for delivery over a guidewire, via alumen from a proximal portion to a distal portion, or via a rapidexchange sidecar in the distal portion of the device (lumen and sidecarnot shown but well known to those of skill in the art). Shaft 110 isshown inserted through introducer 115 which can comprise an endoscope,sheath, or other body introduction device.

Expandable assembly 130 is mounted to a distal portion of shaft 110, andincludes an expandable cage comprising multiple splines 141 which areattached at their distal ends to hub 144 and at their proximal ends tothe distal end of shaft 110. Splines 141 can be resiliently biased in aradially expanded condition, such as stainless steel or nickel titaniumalloy splines biased in the bowed condition shown. Alternatively, one ormore control rods, such as control rod 145, can be used to operablyexpand and/or contract expandable assembly 130, such as when splines 141are biased in a linear configuration. Control rod 145 is attached at itsdistal end to hub 144, and at its proximal end to a control of a handleon the proximal end of shaft 110. Advancement of control rod 145 (e.g.via a knob, lever or other control on the handle) causes expandableassembly 130 to radially collapse or compact, and retraction of controlrod 145 causes expandable assembly 130 to radially expand.

Each spline 141 comprises one or more electrodes, such as electrodes 136and 137 as shown. Each electrode is connected to one or more wires, notshown but configured to deliver monopolar and/or bipolar RF energy toelectrodes 136 and 137, such as to treat at least a portion of targettissue when expandable assembly 130 has been expanded to contact targettissue. After expansion of expandable assembly 130, and performance of afirst energy delivery to target tissue, expandable assembly 130 can berepositioned in a different segment of gastrointestinal tissue, with orwithout radially compacting assembly 130. Subsequently, a second energydelivery can be performed. The steps of repositioning and deliveringenergy are repeated until the desired segment of target tissue istreated in its entirety. In some embodiments, the target tissuecomprises greater than 50% of the length of the duodenal mucosa, orgreater than 90% of the duodenal mucosa length. Alternatively oradditionally, other tissue can be treated, such as has been describedhereabove.

In some embodiments, electrodes 136 and/or 137 are covered with adielectric material, covering 148 as shown in the sectional side view ofa spline 141 illustrated in FIG. 10A. Covering 148 comprises adielectric material such as polytetrafluoroethylene, and is configuredto cause capacitive coupling of electrodes 136 and/or 137 to targettissue. In some embodiments, electrodes 136 and/or 137 comprise a diskshaped electrode and covering 148 comprises a disk-shaped cover withthicker end portions (versus a thinner middle portion), such that thecapacitively coupled RF energy delivered to tissue avoids edge effects(e.g. current concentration along the edge of an electrode 136 and/or137) and results in uniform depth of tissue ablation.

In some embodiments, one or more electrodes 136 and/or 137 are separatedby a thermally conductive, electrically insulating spacer 149, as shownin the sectional side view of a spline 141 illustrated in FIG. 10B.Spacers 149 are positioned between two or more electrodes 136 and/or 137and can comprise a thermally conductive, electrically insulatingmaterial selected from the group consisting of: sapphire; fused quartz;fused silica; a polymeric material; glass; and combinations of these.

Referring now to FIG. 10C, top and side sectional views of an electrodewith a top surface offset from a spline are illustrated, consistent withthe present inventive concepts. Electrode 136 comprises a bottom surfacemounted to spline 141 (e.g. via a weld or swage attachment) and a topsurface positioned at a distance from spline 141, electrode 136 height Has shown. In some embodiments, height H is at least 100 microns, suchthat the top surface of electrode 136 can extend into tissue with anirregular surface such as into villi of the small intestine (e.g. intovilli of the duodenum). In some embodiments, height H is at least 200microns, or at least 400 microns. Electrode 136 height H can be chosento maximize or otherwise improve the amount of electrical energydelivered into tissue.

The sides of electrode 136 (e.g. surfaces relatively orthogonal to orotherwise continuous with the top surface of electrode 136) can besurrounded by an insulating material, such as insulator 148′ as shown.Insulator 148′ can cover some or all of the bottom surface of electrode136. Insulator 148′ can be constructed and arranged such that only thetop surface of electrode 136 is conductive (e.g. to minimize currentdelivered from electrode 136 side and/or bottom surfaces). Insulator148′ can comprise a low-conductivity material, such aspolytetrafluoroethylene, or an electrically insulating coating.

Spline 141 can comprise multiple electrodes 136 with heights similar toheight H such that bipolar RF energy can be delivered between two ormore of the electrodes. Alternatively or additionally, an ablationdevice of the present inventive concepts can comprise multiple splines141 each with at least one electrode 136, such that bipolar RF energycan be delivered between two or more of the splines.

Referring now to FIG. 11, a distal portion of an ablation deviceincluding two expandable elements and intervening conductive filamentsis illustrated, consistent with the present inventive concepts. Ablationdevice 100 comprises shaft 110, a relatively flexible, biocompatible,elongate structure configured for insertion into a body lumen such as alumen of the small intestine (e.g. the lumen of the duodenum). Shaft 110is typically connected to a handle on its proximal end, not shown butconfigured to allow an operator to advance, retract and otherwisemanipulate or control ablation device 100. Ablation device 100 can beconstructed and arranged for delivery over a guidewire, via a lumen froma proximal portion to a distal portion, or via a rapid exchange sidecarin the distal portion of the device (lumen and sidecar not shown butwell known to those of skill in the art). Two expandable assemblies,expandable assemblies 130 a and 130 b, are mounted to a distal portionof shaft 110 as shown. Expandable assemblies 130 a and 130 b cancomprise an inflatable balloon, cage or other expandable element asdescribed in reference to FIG. 1 hereabove. Shaft 110 is shown insertedthrough introducer 115 which can comprise an endoscope, sheath, or otherbody introduction device. Expandable assembly 130 b has been positionedin a portion of duodenal tissue that has had a segment of submucosaltissue expanded (e.g. a full circumferential segment of at least 50% ofthe duodenal submucosa expanded), such as has been described above.

Positioned between expandable assembly 130 a and 130 b is acircumferential array of conductors, electrodes 136. Expandableassemblies 130 a and 130 b and electrodes 136 are positioned andarranged such that when expandable assemblies 130 a and 130 b areradially expanded to contact gastrointestinal wall tissue (e.g. mucosaltissue), electrodes 136 contact tissue. Electrodes 136 are attached toone or more wires, not shown but configured to allow delivery ofmonopolar and/or bipolar by or between and one or more electrodes 136,as has been described hereabove. In some alternative embodiments, one ormore electrodes 136 are positioned on one or more filaments extendingbetween expandable assemblies 130 a and 130 b.

Ablation device 100, or any of the ablation devices of the presentinventive concepts, can be constructed to accommodate over-the-wiredelivery, such as by the inclusion of lumen 114 which exits the distalend of shaft 110 and travels proximally, such as to a guidewireintroduction port, not shown but typically attached to a proximal handleas has been described hereabove.

Referring now to FIG. 12, a distal portion of an ablation deviceincluding rotatable electrodes is illustrated, consistent with thepresent inventive concepts. Ablation device 100 comprises shaft 110, arelatively flexible, biocompatible, elongate structure configured forinsertion into a body lumen such as a lumen of the small intestine (e.g.the lumen of the duodenum). Shaft 110 is typically connected to a handleon its proximal end, not shown but configured to allow an operator toadvance, retract and otherwise manipulate or control ablation device100. Ablation device 100 can be constructed and arranged for deliveryover a guidewire, via a lumen from a proximal portion to a distalportion, or via a rapid exchange sidecar in the distal portion of thedevice (lumen and sidecar not shown but well known to those of skill inthe art). Shaft 110 is shown inserted through introducer 115 which cancomprise an endoscope, sheath, or other body introduction device.

Expandable assembly 130 is mounted to a distal portion of shaft 110, andincludes an expandable cage comprising multiple splines 141 which areattached at their distal ends to hub 144 and at their proximal ends tothe distal end of shaft 110. Splines 141 can be resiliently biased in aradially expanded condition, such as stainless steel or nickel titaniumalloy splines biased in the bowed condition shown. Alternatively, one ormore control rods, such as control rod 145, can be used to operablyexpand and/or contract expandable assembly 130, such as when splines 141are biased in a linear configuration. Control rod 145 is attached at itsdistal end to hub 144, and at its proximal end to a control of a handleon the proximal end of shaft 110. Advancement of control rod 145 (e.g.via a knob, lever or other control on the handle) causes expandableassembly 130 to radially collapse or compact, and retraction of controlrod 145 causes expandable assembly 130 to radially expand. In analternative embodiment, control rod 145 is attached to the proximal endof splines 141, such that advancement of control rod 145 causesexpandable assembly 130 to radially expand, and retraction of controlrod 145 causes expandable assembly 130 to radially compact. As statedabove, radial compression of expandable assembly 130 can be used to stopor reduce delivery of energy to tissue.

Attached to splines 141 are multiple electrodes 136 a-d. Electrodes 136a-d can be rotatably attached to splines 141 via axles 151 as shown.Electrodes 136 a-d are electrically attached to one or more wires, notshown but as described hereabove. Electrodes 136 a-d can be attached tothe one or more wires via axles 151, such as a frictionally engagingelectrical connection that allows electrical energy to be transferredthrough each axle 151 to the associated electrode 136 a-d as theelectrode 136 a-d is rotating. In some embodiments, electrodes 136 a-dare each electrically attached to individual wires such that monopolarand/or bipolar energy can be delivered any of electrodes 136 a-d orbetween any electrodes 136 a-d. When expandable assembly 130 is expandedsuch that electrodes 136 a-d contact tissue (e.g. luminal wall tissue),electrodes 136 a-d are constructed and arranged such that they rotatealong a tissue surface as shaft 110 and/or introducer 115 is advanced orretracted.

A sufficient quantity of electrodes 136 a-d (e.g. one or more on eachspline 141), such as to cover a full circumferential (e.g. approximately360°) axial segment of expandable assembly 130. Alternatively,electrodes 136 a-d can cover a partial circumference (e.g. an areacovering between 45° and 300°) of the outer surface of an axial segmentof expandable assembly 130.

A first energy delivery can be delivered to electrodes 136 a-d, such asto treat target tissue or a portion of target tissue. Subsequently,expandable assembly 130 can be translated axially or distally, and oneor more subsequent energy deliveries performed. In some embodiments, RFenergy is delivered as the electrodes 136 a-d rotate along a tissuesurface. The steps of translating and/or repositioning, and deliveringenergy are repeated until the desired segment of target tissue istreated in its entirety. In some embodiments, the target tissuecomprises greater than 50% of the length of the duodenal mucosa, orgreater than 90% of the duodenal mucosa length. Alternatively oradditionally, other tissue can be treated, such as has been describedhereabove.

The foregoing description and accompanying drawings set forth a numberof examples of representative embodiments at the present time. Variousmodifications, additions and alternative designs will become apparent tothose skilled in the art in light of the foregoing teachings withoutdeparting from the spirit hereof, or exceeding the scope hereof, whichis indicated by the following claims rather than by the foregoingdescription. All changes and variations that fall within the meaning andrange of equivalency of the claims are to be embraced within theirscope.

1. (canceled)
 2. A system for ablating tissue with electrical energycomprising: an ablation device comprising: an elongate shaft with aproximal portion and a distal portion; a radially expandable elementattached to the elongate shaft distal portion; and an ablation elementmounted to the radially expandable element, the ablation elementcomprising a circumferential array of conductors, wherein the ablationelement is constructed and arranged to deliver electrical energy totarget tissue; and an energy delivery unit constructed and arranged todeliver electrical energy to the ablation element of the ablationdevice, wherein the target tissue comprises duodenal mucosal tissue; andwherein the energy delivery unit is configured to deliver the electricalenergy to the ablation element to cause an increase in the temperatureof the target tissue to a setpoint temperature comprising a temperaturebetween 60° C. and 90° C.
 3. The system according to claim 2, whereinthe setpoint temperature comprises a temperature between 65° C. and 90°C.
 4. The system according to claim 2, wherein the setpoint temperaturecomprises a temperature between 75° C. and 85° C.
 5. The systemaccording to claim 2, wherein the system is configured to deliver theelectrical energy to cause non-desiccating ablation of the targettissue.
 6. The system according to claim 2, wherein the ablation devicefurther comprises a fluid delivery element configured to delivermaterial into submucosal tissue to expand the submucosal tissuecircumferentially.
 7. The system according to claim 6, wherein the fluiddelivery element comprises multiple fluid delivery elements.
 8. Thesystem according to claim 7, wherein the ablation device furthercomprises one or more vacuum ports positioned proximate the multiplefluid delivery elements, wherein the vacuum ports are configured toapply a force to the tissue receiving the material.
 9. The systemaccording to claim 2, wherein the ablation element comprises at leastone conductor with a width less than or equal to 1.0 mm.
 10. The systemaccording to claim 9, wherein the at least one conductor comprises awidth between 400 microns and 700 microns.
 11. The system according toclaim 2, wherein the ablation element comprises a first conductor and asecond conductor, wherein the first conductor and the second conductorare positioned with an edge-to-edge spacing between 200 microns and 2mm.
 12. The system according to claim 2, wherein the ablation devicefurther comprises at least one sensor configured to provide a signal.13. The system according to claim 12, wherein the radially expandableelement comprises a balloon, and wherein the signal provided by the atleast one sensor is configured to assess apposition of the balloonagainst the gastrointestinal wall.
 14. The system according to claim 2,wherein the system is constructed and arranged to maintain the tissue atthe set point temperature for approximately 2 seconds to 40 seconds. 15.The system according to claim 14, wherein the system is constructed andarranged to maintain the tissue at the set point temperature forapproximately 15 seconds to 25 seconds.
 16. The system according toclaim 2, wherein the system is constructed and arranged to deliverenergy in at least 2 second energy delivery durations.
 17. The systemaccording to claim 16, wherein the 2 second energy delivery durationscomprise non-continuous delivery of energy for 2 seconds.
 18. The systemaccording to claim 2, wherein the system is configured to limit forceapplied to the duodenal wall to a level at or below 2.5 psi.
 19. Thesystem according to claim 18, wherein the system is configured to limitforce applied to the duodenal wall to a level at or below 1 psi.
 20. Thesystem according to claim 2, wherein the system is configured to causethe radially expandable element to apply a force of at least 0.2 psi tothe duodenal wall during the delivery of electrical energy to the targettissue.
 21. The system according to claim 20, wherein the system isconfigured to cause the radially expandable element to apply a force ofat least 0.5 psi to the duodenal wall during the delivery of electricalenergy to the target tissue.
 22. The system according to claim 2,wherein the system is constructed and arranged to treat a first lengthof duodenum in a first delivery of electrical energy and to treat asecond length of duodenum in a second delivery of electrical energy. 23.The system according to claim 22, wherein the system is constructed andarranged to treat at least three lengths of duodenum with at least threedeliveries of electrical energy.